anno_start	anno_end	anno_text	entity_type	sentence	section
26	31	human	species	Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase	TITLE
32	37	Naa60	protein	Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase	TITLE
39	43	NatF	complex_assembly	Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase	TITLE
78	95	acetyltransferase	protein_type	Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase	TITLE
0	22	N-terminal acetylation	ptm	N-terminal acetylation (Nt-acetylation), carried out by N-terminal acetyltransferases (NATs), is a conserved and primary modification of nascent peptide chains.	ABSTRACT
24	38	Nt-acetylation	ptm	N-terminal acetylation (Nt-acetylation), carried out by N-terminal acetyltransferases (NATs), is a conserved and primary modification of nascent peptide chains.	ABSTRACT
56	85	N-terminal acetyltransferases	protein_type	N-terminal acetylation (Nt-acetylation), carried out by N-terminal acetyltransferases (NATs), is a conserved and primary modification of nascent peptide chains.	ABSTRACT
87	91	NATs	protein_type	N-terminal acetylation (Nt-acetylation), carried out by N-terminal acetyltransferases (NATs), is a conserved and primary modification of nascent peptide chains.	ABSTRACT
145	152	peptide	chemical	N-terminal acetylation (Nt-acetylation), carried out by N-terminal acetyltransferases (NATs), is a conserved and primary modification of nascent peptide chains.	ABSTRACT
0	5	Naa60	protein	Naa60 (also named NatF) is a recently identified NAT found only in multicellular eukaryotes.	ABSTRACT
18	22	NatF	complex_assembly	Naa60 (also named NatF) is a recently identified NAT found only in multicellular eukaryotes.	ABSTRACT
49	52	NAT	protein_type	Naa60 (also named NatF) is a recently identified NAT found only in multicellular eukaryotes.	ABSTRACT
67	91	multicellular eukaryotes	taxonomy_domain	Naa60 (also named NatF) is a recently identified NAT found only in multicellular eukaryotes.	ABSTRACT
80	94	Nt-acetylation	ptm	This protein was shown to locate on the Golgi apparatus and mainly catalyze the Nt-acetylation of transmembrane proteins, and it also harbors lysine Nε-acetyltransferase (KAT) activity to catalyze the acetylation of lysine ε-amine.	ABSTRACT
142	169	lysine Nε-acetyltransferase	protein_type	This protein was shown to locate on the Golgi apparatus and mainly catalyze the Nt-acetylation of transmembrane proteins, and it also harbors lysine Nε-acetyltransferase (KAT) activity to catalyze the acetylation of lysine ε-amine.	ABSTRACT
171	174	KAT	protein_type	This protein was shown to locate on the Golgi apparatus and mainly catalyze the Nt-acetylation of transmembrane proteins, and it also harbors lysine Nε-acetyltransferase (KAT) activity to catalyze the acetylation of lysine ε-amine.	ABSTRACT
201	212	acetylation	ptm	This protein was shown to locate on the Golgi apparatus and mainly catalyze the Nt-acetylation of transmembrane proteins, and it also harbors lysine Nε-acetyltransferase (KAT) activity to catalyze the acetylation of lysine ε-amine.	ABSTRACT
216	222	lysine	residue_name	This protein was shown to locate on the Golgi apparatus and mainly catalyze the Nt-acetylation of transmembrane proteins, and it also harbors lysine Nε-acetyltransferase (KAT) activity to catalyze the acetylation of lysine ε-amine.	ABSTRACT
20	38	crystal structures	evidence	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
42	47	human	species	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
48	53	Naa60	protein	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
55	61	hNaa60	protein	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
63	78	in complex with	protein_state	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
79	96	Acetyl-Coenzyme A	chemical	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
98	104	Ac-CoA	chemical	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
109	119	Coenzyme A	chemical	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
121	124	CoA	chemical	Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA).	ABSTRACT
4	10	hNaa60	protein	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
31	48	amphipathic helix	structure_element	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
63	74	GNAT domain	structure_element	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
120	126	hNaa60	protein	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
136	149	β7-β8 hairpin	structure_element	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
189	195	hNaa60	protein	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
196	201	1-242	residue_range	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
207	220	hNaa60(1-199)	mutant	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
221	239	crystal structures	evidence	The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures.	ABSTRACT
44	50	Phe 34	residue_name_number	Remarkably, we found that the side-chain of Phe 34 can influence the position of the coenzyme, indicating a new regulatory mechanism involving enzyme, co-factor and substrates interactions.	ABSTRACT
85	93	coenzyme	chemical	Remarkably, we found that the side-chain of Phe 34 can influence the position of the coenzyme, indicating a new regulatory mechanism involving enzyme, co-factor and substrates interactions.	ABSTRACT
10	55	structural comparison and biochemical studies	experimental_method	Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved β3-β4 long loop participates in the regulation of hNaa60 activity.	ABSTRACT
71	77	Tyr 97	residue_name_number	Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved β3-β4 long loop participates in the regulation of hNaa60 activity.	ABSTRACT
82	89	His 138	residue_name_number	Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved β3-β4 long loop participates in the regulation of hNaa60 activity.	ABSTRACT
141	154	non-conserved	protein_state	Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved β3-β4 long loop participates in the regulation of hNaa60 activity.	ABSTRACT
155	170	β3-β4 long loop	structure_element	Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved β3-β4 long loop participates in the regulation of hNaa60 activity.	ABSTRACT
205	211	hNaa60	protein	Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved β3-β4 long loop participates in the regulation of hNaa60 activity.	ABSTRACT
0	11	Acetylation	ptm	Acetylation is one of the most ubiquitous modifications that plays a vital role in many biological processes, such as transcriptional regulation, protein-protein interaction, enzyme activity, protein stability, antibiotic resistance, biological rhythm and so on.	INTRO
8	19	acetylation	ptm	Protein acetylation can be grouped into lysine Nε-acetylation and peptide N-terminal acetylation (Nt-acetylation).	INTRO
40	61	lysine Nε-acetylation	ptm	Protein acetylation can be grouped into lysine Nε-acetylation and peptide N-terminal acetylation (Nt-acetylation).	INTRO
66	73	peptide	chemical	Protein acetylation can be grouped into lysine Nε-acetylation and peptide N-terminal acetylation (Nt-acetylation).	INTRO
74	96	N-terminal acetylation	ptm	Protein acetylation can be grouped into lysine Nε-acetylation and peptide N-terminal acetylation (Nt-acetylation).	INTRO
98	112	Nt-acetylation	ptm	Protein acetylation can be grouped into lysine Nε-acetylation and peptide N-terminal acetylation (Nt-acetylation).	INTRO
11	25	Nε-acetylation	ptm	Generally, Nε-acetylation refers to the transfer of an acetyl group from an acetyl coenzyme A (Ac-CoA) to the ε-amino group of lysine.	INTRO
55	61	acetyl	chemical	Generally, Nε-acetylation refers to the transfer of an acetyl group from an acetyl coenzyme A (Ac-CoA) to the ε-amino group of lysine.	INTRO
76	93	acetyl coenzyme A	chemical	Generally, Nε-acetylation refers to the transfer of an acetyl group from an acetyl coenzyme A (Ac-CoA) to the ε-amino group of lysine.	INTRO
95	101	Ac-CoA	chemical	Generally, Nε-acetylation refers to the transfer of an acetyl group from an acetyl coenzyme A (Ac-CoA) to the ε-amino group of lysine.	INTRO
127	133	lysine	residue_name	Generally, Nε-acetylation refers to the transfer of an acetyl group from an acetyl coenzyme A (Ac-CoA) to the ε-amino group of lysine.	INTRO
42	67	lysine acetyltransferases	protein_type	This kind of modification is catalyzed by lysine acetyltransferases (KATs), some of which are named histone acetyltransferases (HATs) because early studies focused mostly on the post-transcriptional acetylation of histones.	INTRO
69	73	KATs	protein_type	This kind of modification is catalyzed by lysine acetyltransferases (KATs), some of which are named histone acetyltransferases (HATs) because early studies focused mostly on the post-transcriptional acetylation of histones.	INTRO
100	126	histone acetyltransferases	protein_type	This kind of modification is catalyzed by lysine acetyltransferases (KATs), some of which are named histone acetyltransferases (HATs) because early studies focused mostly on the post-transcriptional acetylation of histones.	INTRO
128	132	HATs	protein_type	This kind of modification is catalyzed by lysine acetyltransferases (KATs), some of which are named histone acetyltransferases (HATs) because early studies focused mostly on the post-transcriptional acetylation of histones.	INTRO
199	210	acetylation	ptm	This kind of modification is catalyzed by lysine acetyltransferases (KATs), some of which are named histone acetyltransferases (HATs) because early studies focused mostly on the post-transcriptional acetylation of histones.	INTRO
214	222	histones	protein_type	This kind of modification is catalyzed by lysine acetyltransferases (KATs), some of which are named histone acetyltransferases (HATs) because early studies focused mostly on the post-transcriptional acetylation of histones.	INTRO
61	75	Nε-acetylation	ptm	Despite the prominent accomplishments in the field regarding Nε-acetylation by KATs for over 50 years, the significance of the more evolutionarily conserved Nt-acetylation is still inconclusive.	INTRO
79	83	KATs	protein_type	Despite the prominent accomplishments in the field regarding Nε-acetylation by KATs for over 50 years, the significance of the more evolutionarily conserved Nt-acetylation is still inconclusive.	INTRO
157	171	Nt-acetylation	ptm	Despite the prominent accomplishments in the field regarding Nε-acetylation by KATs for over 50 years, the significance of the more evolutionarily conserved Nt-acetylation is still inconclusive.	INTRO
0	14	Nt-acetylation	ptm	Nt-acetylation is an abundant and evolutionarily conserved modification occurring in bacteria, archaea and eukaryotes.	INTRO
85	93	bacteria	taxonomy_domain	Nt-acetylation is an abundant and evolutionarily conserved modification occurring in bacteria, archaea and eukaryotes.	INTRO
95	102	archaea	taxonomy_domain	Nt-acetylation is an abundant and evolutionarily conserved modification occurring in bacteria, archaea and eukaryotes.	INTRO
107	117	eukaryotes	taxonomy_domain	Nt-acetylation is an abundant and evolutionarily conserved modification occurring in bacteria, archaea and eukaryotes.	INTRO
45	50	human	species	It is estimated that about 80–90% of soluble human proteins and 50–70% of yeast proteins are subjected to Nt-acetylation, where an acetyl moiety is transferred from Ac-CoA to the α-amino group of the first residue.	INTRO
74	79	yeast	taxonomy_domain	It is estimated that about 80–90% of soluble human proteins and 50–70% of yeast proteins are subjected to Nt-acetylation, where an acetyl moiety is transferred from Ac-CoA to the α-amino group of the first residue.	INTRO
106	120	Nt-acetylation	ptm	It is estimated that about 80–90% of soluble human proteins and 50–70% of yeast proteins are subjected to Nt-acetylation, where an acetyl moiety is transferred from Ac-CoA to the α-amino group of the first residue.	INTRO
131	137	acetyl	chemical	It is estimated that about 80–90% of soluble human proteins and 50–70% of yeast proteins are subjected to Nt-acetylation, where an acetyl moiety is transferred from Ac-CoA to the α-amino group of the first residue.	INTRO
165	171	Ac-CoA	chemical	It is estimated that about 80–90% of soluble human proteins and 50–70% of yeast proteins are subjected to Nt-acetylation, where an acetyl moiety is transferred from Ac-CoA to the α-amino group of the first residue.	INTRO
34	48	Nt-acetylation	ptm	Recently Nt-acetylome expands the Nt-acetylation to transmembrane proteins.	INTRO
7	21	Nε-acetylation	ptm	Unlike Nε-acetylation that can be eliminated by deacetylases, Nt-acetylation is considered irreversible since no corresponding deacetylase is found to date.	INTRO
48	60	deacetylases	protein_type	Unlike Nε-acetylation that can be eliminated by deacetylases, Nt-acetylation is considered irreversible since no corresponding deacetylase is found to date.	INTRO
62	76	Nt-acetylation	ptm	Unlike Nε-acetylation that can be eliminated by deacetylases, Nt-acetylation is considered irreversible since no corresponding deacetylase is found to date.	INTRO
91	103	irreversible	protein_state	Unlike Nε-acetylation that can be eliminated by deacetylases, Nt-acetylation is considered irreversible since no corresponding deacetylase is found to date.	INTRO
127	138	deacetylase	protein_type	Unlike Nε-acetylation that can be eliminated by deacetylases, Nt-acetylation is considered irreversible since no corresponding deacetylase is found to date.	INTRO
9	23	Nt-acetylation	ptm	Although Nt-acetylation has been regarded as a co-translational modification traditionally, there is evidence that post-translational Nt-acetylation exists.	INTRO
134	148	Nt-acetylation	ptm	Although Nt-acetylation has been regarded as a co-translational modification traditionally, there is evidence that post-translational Nt-acetylation exists.	INTRO
110	124	Nt-acetylation	ptm	During the past decades, a large number of Nt-acetylome researches have shed light on the functional roles of Nt-acetylation, including protein degradation, subcellular localization, protein-protein interaction, protein-membrane interaction, plant development, stress-response and protein stability.	INTRO
242	247	plant	taxonomy_domain	During the past decades, a large number of Nt-acetylome researches have shed light on the functional roles of Nt-acetylation, including protein degradation, subcellular localization, protein-protein interaction, protein-membrane interaction, plant development, stress-response and protein stability.	INTRO
4	18	Nt-acetylation	ptm	The Nt-acetylation is carried out by N-terminal acetyltransferases (NATs) that belong to the GNAT superfamily.	INTRO
37	66	N-terminal acetyltransferases	protein_type	The Nt-acetylation is carried out by N-terminal acetyltransferases (NATs) that belong to the GNAT superfamily.	INTRO
68	72	NATs	protein_type	The Nt-acetylation is carried out by N-terminal acetyltransferases (NATs) that belong to the GNAT superfamily.	INTRO
93	109	GNAT superfamily	protein_type	The Nt-acetylation is carried out by N-terminal acetyltransferases (NATs) that belong to the GNAT superfamily.	INTRO
13	17	NATs	protein_type	To date, six NATs (NatA/B/C/D/E/F) have been identified in eukaryotes.	INTRO
19	23	NatA	complex_assembly	To date, six NATs (NatA/B/C/D/E/F) have been identified in eukaryotes.	INTRO
24	25	B	complex_assembly	To date, six NATs (NatA/B/C/D/E/F) have been identified in eukaryotes.	INTRO
26	27	C	complex_assembly	To date, six NATs (NatA/B/C/D/E/F) have been identified in eukaryotes.	INTRO
28	29	D	complex_assembly	To date, six NATs (NatA/B/C/D/E/F) have been identified in eukaryotes.	INTRO
30	31	E	complex_assembly	To date, six NATs (NatA/B/C/D/E/F) have been identified in eukaryotes.	INTRO
32	33	F	complex_assembly	To date, six NATs (NatA/B/C/D/E/F) have been identified in eukaryotes.	INTRO
59	69	eukaryotes	taxonomy_domain	To date, six NATs (NatA/B/C/D/E/F) have been identified in eukaryotes.	INTRO
20	34	Nt-acetylation	ptm	About 40 percent of Nt-acetylation of soluble proteins in cells is catalyzed by NatA complex which is composed of the catalytic subunit Naa10p and the auxiliary subunit Naa15p.	INTRO
80	84	NatA	complex_assembly	About 40 percent of Nt-acetylation of soluble proteins in cells is catalyzed by NatA complex which is composed of the catalytic subunit Naa10p and the auxiliary subunit Naa15p.	INTRO
136	142	Naa10p	protein	About 40 percent of Nt-acetylation of soluble proteins in cells is catalyzed by NatA complex which is composed of the catalytic subunit Naa10p and the auxiliary subunit Naa15p.	INTRO
169	175	Naa15p	protein	About 40 percent of Nt-acetylation of soluble proteins in cells is catalyzed by NatA complex which is composed of the catalytic subunit Naa10p and the auxiliary subunit Naa15p.	INTRO
0	4	NatE	complex_assembly	NatE was found to physically interact with the NatA complex without any observation of impact on NatA-activity.	INTRO
47	51	NatA	complex_assembly	NatE was found to physically interact with the NatA complex without any observation of impact on NatA-activity.	INTRO
97	101	NatA	complex_assembly	NatE was found to physically interact with the NatA complex without any observation of impact on NatA-activity.	INTRO
34	38	NATs	protein_type	Two other multimeric complexes of NATs are NatB and NatC which contain the catalytic subunits Naa20 and Naa30 and the auxiliary subunits Naa25 and Naa35/Naa38, respectively.	INTRO
43	47	NatB	complex_assembly	Two other multimeric complexes of NATs are NatB and NatC which contain the catalytic subunits Naa20 and Naa30 and the auxiliary subunits Naa25 and Naa35/Naa38, respectively.	INTRO
52	56	NatC	complex_assembly	Two other multimeric complexes of NATs are NatB and NatC which contain the catalytic subunits Naa20 and Naa30 and the auxiliary subunits Naa25 and Naa35/Naa38, respectively.	INTRO
94	99	Naa20	protein	Two other multimeric complexes of NATs are NatB and NatC which contain the catalytic subunits Naa20 and Naa30 and the auxiliary subunits Naa25 and Naa35/Naa38, respectively.	INTRO
104	109	Naa30	protein	Two other multimeric complexes of NATs are NatB and NatC which contain the catalytic subunits Naa20 and Naa30 and the auxiliary subunits Naa25 and Naa35/Naa38, respectively.	INTRO
137	142	Naa25	protein	Two other multimeric complexes of NATs are NatB and NatC which contain the catalytic subunits Naa20 and Naa30 and the auxiliary subunits Naa25 and Naa35/Naa38, respectively.	INTRO
147	152	Naa35	protein	Two other multimeric complexes of NATs are NatB and NatC which contain the catalytic subunits Naa20 and Naa30 and the auxiliary subunits Naa25 and Naa35/Naa38, respectively.	INTRO
153	158	Naa38	protein	Two other multimeric complexes of NATs are NatB and NatC which contain the catalytic subunits Naa20 and Naa30 and the auxiliary subunits Naa25 and Naa35/Naa38, respectively.	INTRO
41	46	Naa40	protein	Furthermore, only the catalytic subunits Naa40 and Naa60 were found for NatD and NatF, respectively.	INTRO
51	56	Naa60	protein	Furthermore, only the catalytic subunits Naa40 and Naa60 were found for NatD and NatF, respectively.	INTRO
72	76	NatD	complex_assembly	Furthermore, only the catalytic subunits Naa40 and Naa60 were found for NatD and NatF, respectively.	INTRO
81	85	NatF	complex_assembly	Furthermore, only the catalytic subunits Naa40 and Naa60 were found for NatD and NatF, respectively.	INTRO
8	22	Nt-acetylation	ptm	Besides Nt-acetylation, accumulating reports have proposed Nε-acetylation carried out by NATs.	INTRO
59	73	Nε-acetylation	ptm	Besides Nt-acetylation, accumulating reports have proposed Nε-acetylation carried out by NATs.	INTRO
89	93	NATs	protein_type	Besides Nt-acetylation, accumulating reports have proposed Nε-acetylation carried out by NATs.	INTRO
53	67	Nt-acetylation	ptm	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
76	81	yeast	taxonomy_domain	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
86	91	human	species	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
147	151	NatF	complex_assembly	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
166	194	N-terminal acetyltransferase	protein_type	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
223	227	NatF	complex_assembly	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
240	245	NAA60	protein	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
264	306	Histone acetyltransferase type B protein 4	protein	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
308	312	HAT4	protein	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
315	320	Naa60	protein	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
324	346	N-acetyltransferase 15	protein	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
348	353	NAT15	protein	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
386	389	NAT	protein_type	There is an evolutionary increasing in the degree of Nt-acetylation between yeast and human which could partly be explained by the contribution of NatF. As the first N-terminal acetyltransferase discovered on an organelle, NatF, encoded by NAA60 and also named as Histone acetyltransferase type B protein 4 (HAT4), Naa60 or N-acetyltransferase 15 (NAT15), is the youngest member of the NAT family.	INTRO
13	17	NATs	protein_type	Unlike other NATs that are highly conserved among lower and higher eukaryotes, NatF only exists in higher eukaryotes.	INTRO
27	43	highly conserved	protein_state	Unlike other NATs that are highly conserved among lower and higher eukaryotes, NatF only exists in higher eukaryotes.	INTRO
50	55	lower	taxonomy_domain	Unlike other NATs that are highly conserved among lower and higher eukaryotes, NatF only exists in higher eukaryotes.	INTRO
60	77	higher eukaryotes	taxonomy_domain	Unlike other NATs that are highly conserved among lower and higher eukaryotes, NatF only exists in higher eukaryotes.	INTRO
79	83	NatF	complex_assembly	Unlike other NATs that are highly conserved among lower and higher eukaryotes, NatF only exists in higher eukaryotes.	INTRO
99	116	higher eukaryotes	taxonomy_domain	Unlike other NATs that are highly conserved among lower and higher eukaryotes, NatF only exists in higher eukaryotes.	INTRO
37	41	NatF	complex_assembly	Subsequent researches indicated that NatF displays its catalytic ability with both Nt-acetylation and lysine Nε-acetylation.	INTRO
83	97	Nt-acetylation	ptm	Subsequent researches indicated that NatF displays its catalytic ability with both Nt-acetylation and lysine Nε-acetylation.	INTRO
102	123	lysine Nε-acetylation	ptm	Subsequent researches indicated that NatF displays its catalytic ability with both Nt-acetylation and lysine Nε-acetylation.	INTRO
6	34	N-terminal acetyltransferase	protein_type	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
36	40	NatF	complex_assembly	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
67	78	acetylation	ptm	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
187	195	Met-Lys-	structure_element	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
197	205	Met-Val-	structure_element	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
207	215	Met-Ala-	structure_element	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
220	228	Met-Met-	structure_element	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
293	297	NatC	complex_assembly	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
302	306	NatE	complex_assembly	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
327	331	NatF	complex_assembly	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
342	366	lysine acetyltransferase	protein_type	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
390	408	lysine acetylation	ptm	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
417	424	histone	protein_type	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
425	427	H4	protein_type	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
439	441	H4	protein_type	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
441	444	K20	residue_name_number	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
446	448	H4	protein_type	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
448	451	K79	residue_name_number	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
456	458	H4	protein_type	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
458	461	K91	residue_name_number	As an N-terminal acetyltransferase, NatF can specifically catalyze acetylation of the N-terminal α-amine of most transmembrane proteins and has substrate preference towards proteins with Met-Lys-, Met-Val-, Met-Ala- and Met-Met-N-termini, thus partially overlapping substrate selectivity with NatC and NatE. On the other hand, NatF, with its lysine acetyltransferase activity, mediates the lysine acetylation of free histone H4, including H4K20, H4K79 and H4K91.	INTRO
29	33	NatF	complex_assembly	Another important feature of NatF is that this protein is anchored on the Golgi apparatus through its C-terminal membrane-integrating region and takes part in the maintaining of Golgi integrity.	INTRO
113	140	membrane-integrating region	structure_element	Another important feature of NatF is that this protein is anchored on the Golgi apparatus through its C-terminal membrane-integrating region and takes part in the maintaining of Golgi integrity.	INTRO
81	85	NatF	complex_assembly	With its unique intracellular organellar localization and substrate selectivity, NatF appears to provide more evolutionary information among the NAT family members.	INTRO
145	148	NAT	protein_type	With its unique intracellular organellar localization and substrate selectivity, NatF appears to provide more evolutionary information among the NAT family members.	INTRO
27	31	NatF	complex_assembly	It was recently found that NatF facilitates nucleosomes assembly and that NAA60 knockdown in MCF7-cell inhibits cell proliferation, sensitizes cells to DNA damage and induces cell apoptosis.	INTRO
44	55	nucleosomes	complex_assembly	It was recently found that NatF facilitates nucleosomes assembly and that NAA60 knockdown in MCF7-cell inhibits cell proliferation, sensitizes cells to DNA damage and induces cell apoptosis.	INTRO
74	79	NAA60	protein	It was recently found that NatF facilitates nucleosomes assembly and that NAA60 knockdown in MCF7-cell inhibits cell proliferation, sensitizes cells to DNA damage and induces cell apoptosis.	INTRO
3	13	Drosophila	taxonomy_domain	In Drosophila cells, NAA60 knockdown induces chromosomal segregation defects during anaphase including lagging chromosomes and chromosomal bridges.	INTRO
21	26	NAA60	protein	In Drosophila cells, NAA60 knockdown induces chromosomal segregation defects during anaphase including lagging chromosomes and chromosomal bridges.	INTRO
66	70	NatF	complex_assembly	Much recent attention has also been focused on the requirement of NatF for regulation of organellar structure.	INTRO
15	20	NAA60	protein	In HeLa cells, NAA60 knockdown causes Golgi apparatus fragmentation which can be rescued by overexpression Naa60.	INTRO
92	106	overexpression	experimental_method	In HeLa cells, NAA60 knockdown causes Golgi apparatus fragmentation which can be rescued by overexpression Naa60.	INTRO
107	112	Naa60	protein	In HeLa cells, NAA60 knockdown causes Golgi apparatus fragmentation which can be rescued by overexpression Naa60.	INTRO
79	83	NATs	protein_type	The systematic investigation of publicly available microarray data showed that NATs share distinct tissue-specific expression patterns in Drosophila and NatF shows a higher expression level in central nervous system of Drosophila.	INTRO
138	148	Drosophila	taxonomy_domain	The systematic investigation of publicly available microarray data showed that NATs share distinct tissue-specific expression patterns in Drosophila and NatF shows a higher expression level in central nervous system of Drosophila.	INTRO
153	157	NatF	complex_assembly	The systematic investigation of publicly available microarray data showed that NATs share distinct tissue-specific expression patterns in Drosophila and NatF shows a higher expression level in central nervous system of Drosophila.	INTRO
219	229	Drosophila	taxonomy_domain	The systematic investigation of publicly available microarray data showed that NATs share distinct tissue-specific expression patterns in Drosophila and NatF shows a higher expression level in central nervous system of Drosophila.	INTRO
18	24	solved	experimental_method	In this study, we solved the structures of human Naa60 (NatF) in complex with coenzyme.	INTRO
29	39	structures	evidence	In this study, we solved the structures of human Naa60 (NatF) in complex with coenzyme.	INTRO
43	48	human	species	In this study, we solved the structures of human Naa60 (NatF) in complex with coenzyme.	INTRO
49	54	Naa60	protein	In this study, we solved the structures of human Naa60 (NatF) in complex with coenzyme.	INTRO
56	60	NatF	complex_assembly	In this study, we solved the structures of human Naa60 (NatF) in complex with coenzyme.	INTRO
62	77	in complex with	protein_state	In this study, we solved the structures of human Naa60 (NatF) in complex with coenzyme.	INTRO
78	86	coenzyme	chemical	In this study, we solved the structures of human Naa60 (NatF) in complex with coenzyme.	INTRO
4	10	hNaa60	protein	The hNaa60 protein contains a unique amphipathic α-helix (α5) following its GNAT domain that might account for the Golgi localization of this protein.	INTRO
37	56	amphipathic α-helix	structure_element	The hNaa60 protein contains a unique amphipathic α-helix (α5) following its GNAT domain that might account for the Golgi localization of this protein.	INTRO
58	60	α5	structure_element	The hNaa60 protein contains a unique amphipathic α-helix (α5) following its GNAT domain that might account for the Golgi localization of this protein.	INTRO
76	87	GNAT domain	structure_element	The hNaa60 protein contains a unique amphipathic α-helix (α5) following its GNAT domain that might account for the Golgi localization of this protein.	INTRO
0	18	Crystal structures	evidence	Crystal structures showed that the β7-β8 hairpin rotated about 50 degrees upon removing the C-terminal region of the protein and this movement substantially changed the geometry of the substrate-binding pocket.	INTRO
35	48	β7-β8 hairpin	structure_element	Crystal structures showed that the β7-β8 hairpin rotated about 50 degrees upon removing the C-terminal region of the protein and this movement substantially changed the geometry of the substrate-binding pocket.	INTRO
92	109	C-terminal region	structure_element	Crystal structures showed that the β7-β8 hairpin rotated about 50 degrees upon removing the C-terminal region of the protein and this movement substantially changed the geometry of the substrate-binding pocket.	INTRO
185	209	substrate-binding pocket	site	Crystal structures showed that the β7-β8 hairpin rotated about 50 degrees upon removing the C-terminal region of the protein and this movement substantially changed the geometry of the substrate-binding pocket.	INTRO
25	31	Phe 34	residue_name_number	Remarkably, we find that Phe 34 may participate in the proper positioning of the coenzyme for the transfer reaction to occur.	INTRO
81	89	coenzyme	chemical	Remarkably, we find that Phe 34 may participate in the proper positioning of the coenzyme for the transfer reaction to occur.	INTRO
8	28	structure comparison	experimental_method	Further structure comparison and biochemical studies also identified other key structural elements essential for the enzyme activity of Naa60.	INTRO
33	52	biochemical studies	experimental_method	Further structure comparison and biochemical studies also identified other key structural elements essential for the enzyme activity of Naa60.	INTRO
136	141	Naa60	protein	Further structure comparison and biochemical studies also identified other key structural elements essential for the enzyme activity of Naa60.	INTRO
8	17	structure	evidence	Overall structure of hNaa60	RESULTS
21	27	hNaa60	protein	Overall structure of hNaa60	RESULTS
88	94	hNaa60	protein	In the effort to prepare the protein for structural studies, we tried a large number of hNaa60 constructs but all failed due to heavy precipitation or aggregation.	RESULTS
0	18	Sequence alignment	experimental_method	Sequence alignment of Naa60 from different species revealed a Glu-Glu-Arg (EER) versus Val-Val-Pro (VVP) sequence difference near the N-terminus of the protein in Xenopus Laevis versus Homo sapiens (Fig. 1A).	RESULTS
22	27	Naa60	protein	Sequence alignment of Naa60 from different species revealed a Glu-Glu-Arg (EER) versus Val-Val-Pro (VVP) sequence difference near the N-terminus of the protein in Xenopus Laevis versus Homo sapiens (Fig. 1A).	RESULTS
62	73	Glu-Glu-Arg	structure_element	Sequence alignment of Naa60 from different species revealed a Glu-Glu-Arg (EER) versus Val-Val-Pro (VVP) sequence difference near the N-terminus of the protein in Xenopus Laevis versus Homo sapiens (Fig. 1A).	RESULTS
75	78	EER	structure_element	Sequence alignment of Naa60 from different species revealed a Glu-Glu-Arg (EER) versus Val-Val-Pro (VVP) sequence difference near the N-terminus of the protein in Xenopus Laevis versus Homo sapiens (Fig. 1A).	RESULTS
87	98	Val-Val-Pro	structure_element	Sequence alignment of Naa60 from different species revealed a Glu-Glu-Arg (EER) versus Val-Val-Pro (VVP) sequence difference near the N-terminus of the protein in Xenopus Laevis versus Homo sapiens (Fig. 1A).	RESULTS
100	103	VVP	structure_element	Sequence alignment of Naa60 from different species revealed a Glu-Glu-Arg (EER) versus Val-Val-Pro (VVP) sequence difference near the N-terminus of the protein in Xenopus Laevis versus Homo sapiens (Fig. 1A).	RESULTS
163	177	Xenopus Laevis	species	Sequence alignment of Naa60 from different species revealed a Glu-Glu-Arg (EER) versus Val-Val-Pro (VVP) sequence difference near the N-terminus of the protein in Xenopus Laevis versus Homo sapiens (Fig. 1A).	RESULTS
185	197	Homo sapiens	species	Sequence alignment of Naa60 from different species revealed a Glu-Glu-Arg (EER) versus Val-Val-Pro (VVP) sequence difference near the N-terminus of the protein in Xenopus Laevis versus Homo sapiens (Fig. 1A).	RESULTS
169	176	mutated	experimental_method	Considering that terminal residues may lack higher-order structure and hydrophobic residues in this region may expose to solvent and hence cause protein aggregation, we mutated residues 4–6 from VVP to EER for the purpose of improving solubility of this protein.	RESULTS
186	189	4–6	residue_range	Considering that terminal residues may lack higher-order structure and hydrophobic residues in this region may expose to solvent and hence cause protein aggregation, we mutated residues 4–6 from VVP to EER for the purpose of improving solubility of this protein.	RESULTS
195	205	VVP to EER	mutant	Considering that terminal residues may lack higher-order structure and hydrophobic residues in this region may expose to solvent and hence cause protein aggregation, we mutated residues 4–6 from VVP to EER for the purpose of improving solubility of this protein.	RESULTS
80	86	hNaa60	protein	According to previous studies, this N-terminal region should not interfere with hNaa60’s Golgi localization.	RESULTS
14	20	hNaa60	protein	We tried many hNaa60 constructs with the three-residues mutation but only the truncated variant 1-199 and the full-length protein behaved well.	RESULTS
56	64	mutation	experimental_method	We tried many hNaa60 constructs with the three-residues mutation but only the truncated variant 1-199 and the full-length protein behaved well.	RESULTS
78	87	truncated	protein_state	We tried many hNaa60 constructs with the three-residues mutation but only the truncated variant 1-199 and the full-length protein behaved well.	RESULTS
96	101	1-199	residue_range	We tried many hNaa60 constructs with the three-residues mutation but only the truncated variant 1-199 and the full-length protein behaved well.	RESULTS
110	121	full-length	protein_state	We tried many hNaa60 constructs with the three-residues mutation but only the truncated variant 1-199 and the full-length protein behaved well.	RESULTS
16	23	crystal	evidence	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
31	40	truncated	protein_state	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
49	54	1-199	residue_range	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
55	70	in complex with	protein_state	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
71	74	CoA	chemical	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
120	127	crystal	evidence	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
135	146	full-length	protein_state	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
174	179	1-242	residue_range	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
181	196	in complex with	protein_state	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
197	203	Ac-CoA	chemical	We obtained the crystal of the truncated variant 1-199 in complex with CoA first, and after extensive trials we got the crystal of the full-length protein (spanning residues 1-242) in complex with Ac-CoA (Fig. 1B,C).	RESULTS
34	41	mutants	protein_state	Hereafter, all deletions or point mutants of hNaa60 we describe here are with the EER mutation.	RESULTS
45	51	hNaa60	protein	Hereafter, all deletions or point mutants of hNaa60 we describe here are with the EER mutation.	RESULTS
82	85	EER	structure_element	Hereafter, all deletions or point mutants of hNaa60 we describe here are with the EER mutation.	RESULTS
86	94	mutation	experimental_method	Hereafter, all deletions or point mutants of hNaa60 we describe here are with the EER mutation.	RESULTS
4	22	crystal structures	evidence	The crystal structures of hNaa60(1-242)/Ac-CoA and hNaa60(1-199)/CoA were determined by molecular replacement and refined to 1.38 Å and 1.60 Å resolution, respectively (Table 1).	RESULTS
26	46	hNaa60(1-242)/Ac-CoA	complex_assembly	The crystal structures of hNaa60(1-242)/Ac-CoA and hNaa60(1-199)/CoA were determined by molecular replacement and refined to 1.38 Å and 1.60 Å resolution, respectively (Table 1).	RESULTS
51	68	hNaa60(1-199)/CoA	complex_assembly	The crystal structures of hNaa60(1-242)/Ac-CoA and hNaa60(1-199)/CoA were determined by molecular replacement and refined to 1.38 Å and 1.60 Å resolution, respectively (Table 1).	RESULTS
88	109	molecular replacement	experimental_method	The crystal structures of hNaa60(1-242)/Ac-CoA and hNaa60(1-199)/CoA were determined by molecular replacement and refined to 1.38 Å and 1.60 Å resolution, respectively (Table 1).	RESULTS
4	25	electron density maps	evidence	The electron density maps were of sufficient quality to trace residues 1-211 of hNaa60(1-242) and residues 5-199 of hNaa60(1-199).	RESULTS
71	76	1-211	residue_range	The electron density maps were of sufficient quality to trace residues 1-211 of hNaa60(1-242) and residues 5-199 of hNaa60(1-199).	RESULTS
80	86	hNaa60	protein	The electron density maps were of sufficient quality to trace residues 1-211 of hNaa60(1-242) and residues 5-199 of hNaa60(1-199).	RESULTS
87	92	1-242	residue_range	The electron density maps were of sufficient quality to trace residues 1-211 of hNaa60(1-242) and residues 5-199 of hNaa60(1-199).	RESULTS
107	112	5-199	residue_range	The electron density maps were of sufficient quality to trace residues 1-211 of hNaa60(1-242) and residues 5-199 of hNaa60(1-199).	RESULTS
116	129	hNaa60(1-199)	mutant	The electron density maps were of sufficient quality to trace residues 1-211 of hNaa60(1-242) and residues 5-199 of hNaa60(1-199).	RESULTS
4	13	structure	evidence	The structure of hNaa60 protein contains a central domain exhibiting a classic GCN5-related N-acetyltransferase (GNAT) folding, along with the extended N- and C-terminal regions (Fig. 1B,C).	RESULTS
17	23	hNaa60	protein	The structure of hNaa60 protein contains a central domain exhibiting a classic GCN5-related N-acetyltransferase (GNAT) folding, along with the extended N- and C-terminal regions (Fig. 1B,C).	RESULTS
43	57	central domain	structure_element	The structure of hNaa60 protein contains a central domain exhibiting a classic GCN5-related N-acetyltransferase (GNAT) folding, along with the extended N- and C-terminal regions (Fig. 1B,C).	RESULTS
79	111	GCN5-related N-acetyltransferase	protein_type	The structure of hNaa60 protein contains a central domain exhibiting a classic GCN5-related N-acetyltransferase (GNAT) folding, along with the extended N- and C-terminal regions (Fig. 1B,C).	RESULTS
113	117	GNAT	protein_type	The structure of hNaa60 protein contains a central domain exhibiting a classic GCN5-related N-acetyltransferase (GNAT) folding, along with the extended N- and C-terminal regions (Fig. 1B,C).	RESULTS
143	151	extended	protein_state	The structure of hNaa60 protein contains a central domain exhibiting a classic GCN5-related N-acetyltransferase (GNAT) folding, along with the extended N- and C-terminal regions (Fig. 1B,C).	RESULTS
152	177	N- and C-terminal regions	structure_element	The structure of hNaa60 protein contains a central domain exhibiting a classic GCN5-related N-acetyltransferase (GNAT) folding, along with the extended N- and C-terminal regions (Fig. 1B,C).	RESULTS
4	18	central domain	structure_element	The central domain includes nine β strands (β1-β9) and four α-helixes (α1-α4) and is highly similar to the known hNaa50p and other reported NATs (Fig. 1D).	RESULTS
33	42	β strands	structure_element	The central domain includes nine β strands (β1-β9) and four α-helixes (α1-α4) and is highly similar to the known hNaa50p and other reported NATs (Fig. 1D).	RESULTS
44	49	β1-β9	structure_element	The central domain includes nine β strands (β1-β9) and four α-helixes (α1-α4) and is highly similar to the known hNaa50p and other reported NATs (Fig. 1D).	RESULTS
60	69	α-helixes	structure_element	The central domain includes nine β strands (β1-β9) and four α-helixes (α1-α4) and is highly similar to the known hNaa50p and other reported NATs (Fig. 1D).	RESULTS
71	76	α1-α4	structure_element	The central domain includes nine β strands (β1-β9) and four α-helixes (α1-α4) and is highly similar to the known hNaa50p and other reported NATs (Fig. 1D).	RESULTS
85	99	highly similar	protein_state	The central domain includes nine β strands (β1-β9) and four α-helixes (α1-α4) and is highly similar to the known hNaa50p and other reported NATs (Fig. 1D).	RESULTS
113	120	hNaa50p	protein	The central domain includes nine β strands (β1-β9) and four α-helixes (α1-α4) and is highly similar to the known hNaa50p and other reported NATs (Fig. 1D).	RESULTS
140	144	NATs	protein_type	The central domain includes nine β strands (β1-β9) and four α-helixes (α1-α4) and is highly similar to the known hNaa50p and other reported NATs (Fig. 1D).	RESULTS
12	18	hNaa60	protein	However, in hNaa60, there is an extra 20-residue loop between β3 and β4 that forms a small subdomain with well-defined 3D structure (Fig. 1B–D).	RESULTS
32	53	extra 20-residue loop	structure_element	However, in hNaa60, there is an extra 20-residue loop between β3 and β4 that forms a small subdomain with well-defined 3D structure (Fig. 1B–D).	RESULTS
62	64	β3	structure_element	However, in hNaa60, there is an extra 20-residue loop between β3 and β4 that forms a small subdomain with well-defined 3D structure (Fig. 1B–D).	RESULTS
69	71	β4	structure_element	However, in hNaa60, there is an extra 20-residue loop between β3 and β4 that forms a small subdomain with well-defined 3D structure (Fig. 1B–D).	RESULTS
85	100	small subdomain	structure_element	However, in hNaa60, there is an extra 20-residue loop between β3 and β4 that forms a small subdomain with well-defined 3D structure (Fig. 1B–D).	RESULTS
17	30	β7-β8 strands	structure_element	Furthermore, the β7-β8 strands form an approximately antiparallel β-hairpin structure remarkably different from that in hNaa50p (Fig. 1D).	RESULTS
39	85	approximately antiparallel β-hairpin structure	structure_element	Furthermore, the β7-β8 strands form an approximately antiparallel β-hairpin structure remarkably different from that in hNaa50p (Fig. 1D).	RESULTS
120	127	hNaa50p	protein	Furthermore, the β7-β8 strands form an approximately antiparallel β-hairpin structure remarkably different from that in hNaa50p (Fig. 1D).	RESULTS
4	29	N- and C-terminal regions	structure_element	The N- and C-terminal regions form helical structures (α0 and α5) stretching out from the central GCN5-domain (Fig. 1C).	RESULTS
35	53	helical structures	structure_element	The N- and C-terminal regions form helical structures (α0 and α5) stretching out from the central GCN5-domain (Fig. 1C).	RESULTS
55	57	α0	structure_element	The N- and C-terminal regions form helical structures (α0 and α5) stretching out from the central GCN5-domain (Fig. 1C).	RESULTS
62	64	α5	structure_element	The N- and C-terminal regions form helical structures (α0 and α5) stretching out from the central GCN5-domain (Fig. 1C).	RESULTS
98	109	GCN5-domain	structure_element	The N- and C-terminal regions form helical structures (α0 and α5) stretching out from the central GCN5-domain (Fig. 1C).	RESULTS
55	61	hNaa60	protein	Interestingly, we found that the catalytic activity of hNaa60(1-242) is much lower than that of hNaa60(1-199) (Figure S1), indicating that residues 200–242 may have some auto-inhibitory effect on the activity of the enzyme.	RESULTS
62	67	1-242	residue_range	Interestingly, we found that the catalytic activity of hNaa60(1-242) is much lower than that of hNaa60(1-199) (Figure S1), indicating that residues 200–242 may have some auto-inhibitory effect on the activity of the enzyme.	RESULTS
96	109	hNaa60(1-199)	mutant	Interestingly, we found that the catalytic activity of hNaa60(1-242) is much lower than that of hNaa60(1-199) (Figure S1), indicating that residues 200–242 may have some auto-inhibitory effect on the activity of the enzyme.	RESULTS
148	155	200–242	residue_range	Interestingly, we found that the catalytic activity of hNaa60(1-242) is much lower than that of hNaa60(1-199) (Figure S1), indicating that residues 200–242 may have some auto-inhibitory effect on the activity of the enzyme.	RESULTS
50	56	hNaa60	protein	However, since this region was not visible in the hNaa60(1-242) crystal structure, we do not yet understand how this happens.	RESULTS
57	62	1-242	residue_range	However, since this region was not visible in the hNaa60(1-242) crystal structure, we do not yet understand how this happens.	RESULTS
64	81	crystal structure	evidence	However, since this region was not visible in the hNaa60(1-242) crystal structure, we do not yet understand how this happens.	RESULTS
34	40	hNaa60	protein	Another possibility is that since hNaa60 is localized on Golgi apparatus, the observed low activity of the full-length hNaa60 might be related to lack of Golgi localization of the enzyme in our in vitro studies.	RESULTS
107	118	full-length	protein_state	Another possibility is that since hNaa60 is localized on Golgi apparatus, the observed low activity of the full-length hNaa60 might be related to lack of Golgi localization of the enzyme in our in vitro studies.	RESULTS
119	125	hNaa60	protein	Another possibility is that since hNaa60 is localized on Golgi apparatus, the observed low activity of the full-length hNaa60 might be related to lack of Golgi localization of the enzyme in our in vitro studies.	RESULTS
48	55	mutants	protein_state	For the convenience of studying the kinetics of mutants, the mutagenesis studies described hereafter were all based on hNaa60 (1-199).	RESULTS
61	80	mutagenesis studies	experimental_method	For the convenience of studying the kinetics of mutants, the mutagenesis studies described hereafter were all based on hNaa60 (1-199).	RESULTS
119	133	hNaa60 (1-199)	mutant	For the convenience of studying the kinetics of mutants, the mutagenesis studies described hereafter were all based on hNaa60 (1-199).	RESULTS
3	22	amphipathic α-helix	structure_element	An amphipathic α-helix in the C-terminal region may contribute to Golgi localization of hNaa60	RESULTS
30	47	C-terminal region	structure_element	An amphipathic α-helix in the C-terminal region may contribute to Golgi localization of hNaa60	RESULTS
88	94	hNaa60	protein	An amphipathic α-helix in the C-terminal region may contribute to Golgi localization of hNaa60	RESULTS
13	19	hNaa60	protein	There is one hNaa60 molecule in the asymmetric unit in the hNaa60(1-242)/Ac-CoA structure.	RESULTS
59	79	hNaa60(1-242)/Ac-CoA	complex_assembly	There is one hNaa60 molecule in the asymmetric unit in the hNaa60(1-242)/Ac-CoA structure.	RESULTS
80	89	structure	evidence	There is one hNaa60 molecule in the asymmetric unit in the hNaa60(1-242)/Ac-CoA structure.	RESULTS
4	21	C-terminal region	structure_element	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
40	51	GCN5-domain	structure_element	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
61	78	amphipathic helix	structure_element	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
80	82	α5	structure_element	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
152	176	hydrophobic interactions	bond_interaction	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
185	193	α5-helix	structure_element	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
200	218	hydrophobic groove	site	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
242	244	β1	structure_element	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
249	259	β3 strands	structure_element	The C-terminal region extended from the GCN5-domain forms an amphipathic helix (α5) and interacts with a molecule in a neighbor asymmetric unit through hydrophobic interactions between α5-helix and a hydrophobic groove between the N-terminal β1 and β3 strands of the neighbor molecule (Fig. 2A).	RESULTS
4	24	C-terminal extension	structure_element	The C-terminal extension following α5-helix forms a β-turn that wraps around and interacts with the neighbor protein molecule through hydrophobic interactions, too.	RESULTS
35	43	α5-helix	structure_element	The C-terminal extension following α5-helix forms a β-turn that wraps around and interacts with the neighbor protein molecule through hydrophobic interactions, too.	RESULTS
52	58	β-turn	structure_element	The C-terminal extension following α5-helix forms a β-turn that wraps around and interacts with the neighbor protein molecule through hydrophobic interactions, too.	RESULTS
134	158	hydrophobic interactions	bond_interaction	The C-terminal extension following α5-helix forms a β-turn that wraps around and interacts with the neighbor protein molecule through hydrophobic interactions, too.	RESULTS
7	24	hNaa60(1-199)/CoA	complex_assembly	In the hNaa60(1-199)/CoA structure, a part of the α5-helix is deleted due to truncation of the C-terminal region (Fig. 1B).	RESULTS
25	34	structure	evidence	In the hNaa60(1-199)/CoA structure, a part of the α5-helix is deleted due to truncation of the C-terminal region (Fig. 1B).	RESULTS
50	58	α5-helix	structure_element	In the hNaa60(1-199)/CoA structure, a part of the α5-helix is deleted due to truncation of the C-terminal region (Fig. 1B).	RESULTS
95	112	C-terminal region	structure_element	In the hNaa60(1-199)/CoA structure, a part of the α5-helix is deleted due to truncation of the C-terminal region (Fig. 1B).	RESULTS
41	49	α5-helix	structure_element	Interestingly, the remaining residues in α5-helix still form an amphipathic helix although the hydrophobic interaction with the N-terminal hydrophobic groove of a neighbor molecule is abolished and the helix is largely exposed in solvent due to different crystal packing (Fig. 2B).	RESULTS
64	81	amphipathic helix	structure_element	Interestingly, the remaining residues in α5-helix still form an amphipathic helix although the hydrophobic interaction with the N-terminal hydrophobic groove of a neighbor molecule is abolished and the helix is largely exposed in solvent due to different crystal packing (Fig. 2B).	RESULTS
95	118	hydrophobic interaction	bond_interaction	Interestingly, the remaining residues in α5-helix still form an amphipathic helix although the hydrophobic interaction with the N-terminal hydrophobic groove of a neighbor molecule is abolished and the helix is largely exposed in solvent due to different crystal packing (Fig. 2B).	RESULTS
139	157	hydrophobic groove	site	Interestingly, the remaining residues in α5-helix still form an amphipathic helix although the hydrophobic interaction with the N-terminal hydrophobic groove of a neighbor molecule is abolished and the helix is largely exposed in solvent due to different crystal packing (Fig. 2B).	RESULTS
202	207	helix	structure_element	Interestingly, the remaining residues in α5-helix still form an amphipathic helix although the hydrophobic interaction with the N-terminal hydrophobic groove of a neighbor molecule is abolished and the helix is largely exposed in solvent due to different crystal packing (Fig. 2B).	RESULTS
255	270	crystal packing	evidence	Interestingly, the remaining residues in α5-helix still form an amphipathic helix although the hydrophobic interaction with the N-terminal hydrophobic groove of a neighbor molecule is abolished and the helix is largely exposed in solvent due to different crystal packing (Fig. 2B).	RESULTS
39	46	182–216	residue_range	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
85	91	hNaa60	protein	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
119	128	structure	evidence	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
134	149	solvent-exposed	protein_state	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
150	167	amphipathic helix	structure_element	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
169	171	α5	structure_element	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
192	199	190-202	residue_range	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
259	266	Ile 190	residue_name_number	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
268	275	Leu 191	residue_name_number	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
277	284	Ile 194	residue_name_number	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
286	293	Leu 197	residue_name_number	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
298	305	Leu 201	residue_name_number	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
398	404	hNaa60	protein	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
579	587	KalSec14	protein	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
589	593	Atg3	protein	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
595	601	PB1-F2	protein	A recent research showed that residues 182–216 are important for the localization of hNaa60 on Golgi. According to our structure, the solvent-exposed amphipathic helix (α5) formed by residues 190-202 with an array of hydrophobic residues located on one side (Ile 190, Leu 191, Ile 194, Leu 197 and Leu 201) and hydrophilic residues on the other side (Fig. S2) might account for interaction between hNaa60 and Golgi membrane, as it is a typical structure accounting for membrane association through immersing into the lipid bi-layer with its hydrophobic side as was observed with KalSec14, Atg3, PB1-F2 etc.	RESULTS
4	17	β7-β8 hairpin	structure_element	The β7-β8 hairpin showed alternative conformations in the hNaa60 crystal structures	RESULTS
58	64	hNaa60	protein	The β7-β8 hairpin showed alternative conformations in the hNaa60 crystal structures	RESULTS
65	83	crystal structures	evidence	The β7-β8 hairpin showed alternative conformations in the hNaa60 crystal structures	RESULTS
0	13	Superposition	experimental_method	Superposition of hNaa60(1-242)/Ac-CoA, hNaa60(1-199)/CoA and hNaa50/CoA/peptide (PDB 3TFY) revealed considerable difference in the β7-β8 hairpin region despite the overall stability and similarity of the GNAT domain (Fig. 1D).	RESULTS
17	37	hNaa60(1-242)/Ac-CoA	complex_assembly	Superposition of hNaa60(1-242)/Ac-CoA, hNaa60(1-199)/CoA and hNaa50/CoA/peptide (PDB 3TFY) revealed considerable difference in the β7-β8 hairpin region despite the overall stability and similarity of the GNAT domain (Fig. 1D).	RESULTS
39	56	hNaa60(1-199)/CoA	complex_assembly	Superposition of hNaa60(1-242)/Ac-CoA, hNaa60(1-199)/CoA and hNaa50/CoA/peptide (PDB 3TFY) revealed considerable difference in the β7-β8 hairpin region despite the overall stability and similarity of the GNAT domain (Fig. 1D).	RESULTS
61	79	hNaa50/CoA/peptide	complex_assembly	Superposition of hNaa60(1-242)/Ac-CoA, hNaa60(1-199)/CoA and hNaa50/CoA/peptide (PDB 3TFY) revealed considerable difference in the β7-β8 hairpin region despite the overall stability and similarity of the GNAT domain (Fig. 1D).	RESULTS
131	144	β7-β8 hairpin	structure_element	Superposition of hNaa60(1-242)/Ac-CoA, hNaa60(1-199)/CoA and hNaa50/CoA/peptide (PDB 3TFY) revealed considerable difference in the β7-β8 hairpin region despite the overall stability and similarity of the GNAT domain (Fig. 1D).	RESULTS
204	215	GNAT domain	structure_element	Superposition of hNaa60(1-242)/Ac-CoA, hNaa60(1-199)/CoA and hNaa50/CoA/peptide (PDB 3TFY) revealed considerable difference in the β7-β8 hairpin region despite the overall stability and similarity of the GNAT domain (Fig. 1D).	RESULTS
3	9	hNaa60	protein	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
10	15	1-242	residue_range	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
22	35	β7-β8 hairpin	structure_element	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
73	83	α1-α2 loop	structure_element	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
109	131	substrate binding site	site	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
145	151	hNaa50	protein	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
185	193	flexible	protein_state	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
194	198	loop	structure_element	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
213	223	β6-β7 loop	structure_element	In hNaa60(1-242), the β7-β8 hairpin is located in close proximity to the α1-α2 loop, creating a more compact substrate binding site than that in hNaa50, where this region adopts a more flexible loop conformation (β6-β7 loop).	RESULTS
5	13	removing	experimental_method	Upon removing the C-terminal region of hNaa60, we observed that hNaa60 (1-199) molecules pack in a different way involving the β7-β8 hairpin in the crystal, leading to about 50 degree rotation of the hairpin which moves away from the α1-α2 loop (Figs 1D and 2C).	RESULTS
18	35	C-terminal region	structure_element	Upon removing the C-terminal region of hNaa60, we observed that hNaa60 (1-199) molecules pack in a different way involving the β7-β8 hairpin in the crystal, leading to about 50 degree rotation of the hairpin which moves away from the α1-α2 loop (Figs 1D and 2C).	RESULTS
39	45	hNaa60	protein	Upon removing the C-terminal region of hNaa60, we observed that hNaa60 (1-199) molecules pack in a different way involving the β7-β8 hairpin in the crystal, leading to about 50 degree rotation of the hairpin which moves away from the α1-α2 loop (Figs 1D and 2C).	RESULTS
64	78	hNaa60 (1-199)	mutant	Upon removing the C-terminal region of hNaa60, we observed that hNaa60 (1-199) molecules pack in a different way involving the β7-β8 hairpin in the crystal, leading to about 50 degree rotation of the hairpin which moves away from the α1-α2 loop (Figs 1D and 2C).	RESULTS
127	140	β7-β8 hairpin	structure_element	Upon removing the C-terminal region of hNaa60, we observed that hNaa60 (1-199) molecules pack in a different way involving the β7-β8 hairpin in the crystal, leading to about 50 degree rotation of the hairpin which moves away from the α1-α2 loop (Figs 1D and 2C).	RESULTS
148	155	crystal	evidence	Upon removing the C-terminal region of hNaa60, we observed that hNaa60 (1-199) molecules pack in a different way involving the β7-β8 hairpin in the crystal, leading to about 50 degree rotation of the hairpin which moves away from the α1-α2 loop (Figs 1D and 2C).	RESULTS
200	207	hairpin	structure_element	Upon removing the C-terminal region of hNaa60, we observed that hNaa60 (1-199) molecules pack in a different way involving the β7-β8 hairpin in the crystal, leading to about 50 degree rotation of the hairpin which moves away from the α1-α2 loop (Figs 1D and 2C).	RESULTS
234	244	α1-α2 loop	structure_element	Upon removing the C-terminal region of hNaa60, we observed that hNaa60 (1-199) molecules pack in a different way involving the β7-β8 hairpin in the crystal, leading to about 50 degree rotation of the hairpin which moves away from the α1-α2 loop (Figs 1D and 2C).	RESULTS
69	91	substrate binding site	site	This conformational change substantially altered the geometry of the substrate binding site, which could potentially change the way in which the substrate accesses the active site of the enzyme.	RESULTS
168	179	active site	site	This conformational change substantially altered the geometry of the substrate binding site, which could potentially change the way in which the substrate accesses the active site of the enzyme.	RESULTS
3	9	hNaa60	protein	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
10	15	1-242	residue_range	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
22	35	β7-β8 hairpin	structure_element	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
47	58	active site	site	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
96	102	hNaa50	protein	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
168	179	active site	site	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
231	237	tunnel	site	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
244	250	Ac-CoA	chemical	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
251	254	CoA	chemical	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
306	309	NAT	protein_type	In hNaa60(1-242), the β7-β8 hairpin covers the active site in a way similar to that observed in hNaa50, presumably leaving only one way for the substrate to access the active site, i.e. to enter from the opposite end into the same tunnel where Ac-CoA/CoA binds (Fig. 2D), which may accommodate access of a NAT substrate only.	RESULTS
0	3	KAT	protein_type	KAT activity of hNaa60 toward histone H4 has been noted in previous study, and our enzyme kinetic data also indicated that hNaa60 can acetylate H3-H4 tetramer in vitro (Figure S3).	RESULTS
16	22	hNaa60	protein	KAT activity of hNaa60 toward histone H4 has been noted in previous study, and our enzyme kinetic data also indicated that hNaa60 can acetylate H3-H4 tetramer in vitro (Figure S3).	RESULTS
30	37	histone	protein_type	KAT activity of hNaa60 toward histone H4 has been noted in previous study, and our enzyme kinetic data also indicated that hNaa60 can acetylate H3-H4 tetramer in vitro (Figure S3).	RESULTS
38	40	H4	protein_type	KAT activity of hNaa60 toward histone H4 has been noted in previous study, and our enzyme kinetic data also indicated that hNaa60 can acetylate H3-H4 tetramer in vitro (Figure S3).	RESULTS
83	102	enzyme kinetic data	evidence	KAT activity of hNaa60 toward histone H4 has been noted in previous study, and our enzyme kinetic data also indicated that hNaa60 can acetylate H3-H4 tetramer in vitro (Figure S3).	RESULTS
123	129	hNaa60	protein	KAT activity of hNaa60 toward histone H4 has been noted in previous study, and our enzyme kinetic data also indicated that hNaa60 can acetylate H3-H4 tetramer in vitro (Figure S3).	RESULTS
144	149	H3-H4	complex_assembly	KAT activity of hNaa60 toward histone H4 has been noted in previous study, and our enzyme kinetic data also indicated that hNaa60 can acetylate H3-H4 tetramer in vitro (Figure S3).	RESULTS
150	158	tetramer	oligomeric_state	KAT activity of hNaa60 toward histone H4 has been noted in previous study, and our enzyme kinetic data also indicated that hNaa60 can acetylate H3-H4 tetramer in vitro (Figure S3).	RESULTS
29	40	acetylation	ptm	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
51	58	histone	protein_type	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
59	64	H3-H4	complex_assembly	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
65	73	tetramer	oligomeric_state	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
80	97	mass spectrometry	experimental_method	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
125	131	lysine	residue_name	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
187	198	acetylation	ptm	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
217	228	acetylation	ptm	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
257	270	hNaa60(1-199)	mutant	Furthermore, we analyzed the acetylation status of histone H3-H4 tetramer using mass spectrometry and observed that multiple lysine residues in the protein showed significantly increased acetylation level and changed acetylation profile upon treatment with hNaa60(1-199) (Figure S4).	RESULTS
18	64	liquid chromatography-tandem mass spectrometry	experimental_method	We also conducted liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis on a synthetic peptide (NH2-MKGKEEKEGGAR-COOH) after treatment with hNaa60(1-199), and the data confirmed that both the N-terminal α-amine and lysine side-chain ε-amine were robustly acetylated after the treatment (Table S1).	RESULTS
66	74	LC/MS/MS	experimental_method	We also conducted liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis on a synthetic peptide (NH2-MKGKEEKEGGAR-COOH) after treatment with hNaa60(1-199), and the data confirmed that both the N-terminal α-amine and lysine side-chain ε-amine were robustly acetylated after the treatment (Table S1).	RESULTS
100	107	peptide	chemical	We also conducted liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis on a synthetic peptide (NH2-MKGKEEKEGGAR-COOH) after treatment with hNaa60(1-199), and the data confirmed that both the N-terminal α-amine and lysine side-chain ε-amine were robustly acetylated after the treatment (Table S1).	RESULTS
109	130	NH2-MKGKEEKEGGAR-COOH	chemical	We also conducted liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis on a synthetic peptide (NH2-MKGKEEKEGGAR-COOH) after treatment with hNaa60(1-199), and the data confirmed that both the N-terminal α-amine and lysine side-chain ε-amine were robustly acetylated after the treatment (Table S1).	RESULTS
153	166	hNaa60(1-199)	mutant	We also conducted liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis on a synthetic peptide (NH2-MKGKEEKEGGAR-COOH) after treatment with hNaa60(1-199), and the data confirmed that both the N-terminal α-amine and lysine side-chain ε-amine were robustly acetylated after the treatment (Table S1).	RESULTS
228	234	lysine	residue_name	We also conducted liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis on a synthetic peptide (NH2-MKGKEEKEGGAR-COOH) after treatment with hNaa60(1-199), and the data confirmed that both the N-terminal α-amine and lysine side-chain ε-amine were robustly acetylated after the treatment (Table S1).	RESULTS
268	278	acetylated	protein_state	We also conducted liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis on a synthetic peptide (NH2-MKGKEEKEGGAR-COOH) after treatment with hNaa60(1-199), and the data confirmed that both the N-terminal α-amine and lysine side-chain ε-amine were robustly acetylated after the treatment (Table S1).	RESULTS
7	31	structural investigation	experimental_method	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
41	45	NATs	protein_type	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
64	74	β6-β7 loop	structure_element	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
97	110	β7-β8 hairpin	structure_element	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
114	120	hNaa60	protein	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
130	140	α1-α2 loop	structure_element	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
154	176	substrate-binding site	site	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
180	184	NATs	protein_type	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
198	204	lysine	residue_name	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
223	226	KAT	protein_type	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
262	273	active site	site	Recent structural investigation of other NATs proposed that the β6-β7 loop, corresponding to the β7-β8 hairpin in hNaa60, and the α1-α2 loop flanking the substrate-binding site of NATs, prevent the lysine side-chain of the KAT substrates from inserting into the active site.	RESULTS
8	21	superposition	experimental_method	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
25	31	hNaa60	protein	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
32	37	1-242	residue_range	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
39	48	structure	evidence	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
60	65	Hat1p	protein	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
77	80	KAT	protein_type	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
82	97	in complex with	protein_state	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
100	107	histone	protein_type	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
108	110	H4	protein_type	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
111	118	peptide	chemical	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
164	166	H4	protein_type	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
167	174	peptide	chemical	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
178	181	KAT	protein_type	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
202	215	β7-β8 hairpin	structure_element	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
219	225	hNaa60	protein	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
226	231	1-242	residue_range	Indeed, superposition of hNaa60(1-242) structure on that of Hat1p, a typical KAT, in complex with a histone H4 peptide revealed obvious overlapping/clashing of the H4 peptide (a KAT substrate) with the β7-β8 hairpin of hNaa60(1-242) (Fig. 2D).	RESULTS
22	35	hNaa60(1-199)	mutant	Interestingly, in the hNaa60(1-199) crystal structure, the displaced β7-β8 hairpin opened a second way for the substrate to access the active center that would readily accommodate the binding of the H4 peptide (Fig. 2E), thus implied a potential explanation for KAT activity of this enzyme from a structural biological view.	RESULTS
36	53	crystal structure	evidence	Interestingly, in the hNaa60(1-199) crystal structure, the displaced β7-β8 hairpin opened a second way for the substrate to access the active center that would readily accommodate the binding of the H4 peptide (Fig. 2E), thus implied a potential explanation for KAT activity of this enzyme from a structural biological view.	RESULTS
69	82	β7-β8 hairpin	structure_element	Interestingly, in the hNaa60(1-199) crystal structure, the displaced β7-β8 hairpin opened a second way for the substrate to access the active center that would readily accommodate the binding of the H4 peptide (Fig. 2E), thus implied a potential explanation for KAT activity of this enzyme from a structural biological view.	RESULTS
135	148	active center	site	Interestingly, in the hNaa60(1-199) crystal structure, the displaced β7-β8 hairpin opened a second way for the substrate to access the active center that would readily accommodate the binding of the H4 peptide (Fig. 2E), thus implied a potential explanation for KAT activity of this enzyme from a structural biological view.	RESULTS
199	201	H4	protein_type	Interestingly, in the hNaa60(1-199) crystal structure, the displaced β7-β8 hairpin opened a second way for the substrate to access the active center that would readily accommodate the binding of the H4 peptide (Fig. 2E), thus implied a potential explanation for KAT activity of this enzyme from a structural biological view.	RESULTS
202	209	peptide	chemical	Interestingly, in the hNaa60(1-199) crystal structure, the displaced β7-β8 hairpin opened a second way for the substrate to access the active center that would readily accommodate the binding of the H4 peptide (Fig. 2E), thus implied a potential explanation for KAT activity of this enzyme from a structural biological view.	RESULTS
262	265	KAT	protein_type	Interestingly, in the hNaa60(1-199) crystal structure, the displaced β7-β8 hairpin opened a second way for the substrate to access the active center that would readily accommodate the binding of the H4 peptide (Fig. 2E), thus implied a potential explanation for KAT activity of this enzyme from a structural biological view.	RESULTS
15	21	hNaa60	protein	However, since hNaa60(1-242) and hNaa60(1-199) were crystallized in different crystal forms, the observed conformational change of the β7-β8 hairpin may simply be an artifact related to the different crystal packing.	RESULTS
22	27	1-242	residue_range	However, since hNaa60(1-242) and hNaa60(1-199) were crystallized in different crystal forms, the observed conformational change of the β7-β8 hairpin may simply be an artifact related to the different crystal packing.	RESULTS
33	39	hNaa60	protein	However, since hNaa60(1-242) and hNaa60(1-199) were crystallized in different crystal forms, the observed conformational change of the β7-β8 hairpin may simply be an artifact related to the different crystal packing.	RESULTS
52	64	crystallized	experimental_method	However, since hNaa60(1-242) and hNaa60(1-199) were crystallized in different crystal forms, the observed conformational change of the β7-β8 hairpin may simply be an artifact related to the different crystal packing.	RESULTS
78	91	crystal forms	evidence	However, since hNaa60(1-242) and hNaa60(1-199) were crystallized in different crystal forms, the observed conformational change of the β7-β8 hairpin may simply be an artifact related to the different crystal packing.	RESULTS
135	148	β7-β8 hairpin	structure_element	However, since hNaa60(1-242) and hNaa60(1-199) were crystallized in different crystal forms, the observed conformational change of the β7-β8 hairpin may simply be an artifact related to the different crystal packing.	RESULTS
200	215	crystal packing	evidence	However, since hNaa60(1-242) and hNaa60(1-199) were crystallized in different crystal forms, the observed conformational change of the β7-β8 hairpin may simply be an artifact related to the different crystal packing.	RESULTS
12	15	KAT	protein_type	Whether the KAT substrates bind to the β7-β8 hairpin displaced conformation of the enzyme needs to be verified by further structural and functional studies.	RESULTS
39	52	β7-β8 hairpin	structure_element	Whether the KAT substrates bind to the β7-β8 hairpin displaced conformation of the enzyme needs to be verified by further structural and functional studies.	RESULTS
122	155	structural and functional studies	experimental_method	Whether the KAT substrates bind to the β7-β8 hairpin displaced conformation of the enzyme needs to be verified by further structural and functional studies.	RESULTS
0	6	Phe 34	residue_name_number	Phe 34 facilitates proper positioning of the cofactor for acetyl-transfer	RESULTS
58	64	acetyl	chemical	Phe 34 facilitates proper positioning of the cofactor for acetyl-transfer	RESULTS
4	20	electron density	evidence	The electron density of Phe 34 side-chain is well defined in the hNaa60(1-242)/Ac-CoA structure, but becomes invisible in the hNaa60(1-199)/CoA structure, indicating displacement of the Phe 34 side-chain in the latter (Fig. 3A,B).	RESULTS
24	30	Phe 34	residue_name_number	The electron density of Phe 34 side-chain is well defined in the hNaa60(1-242)/Ac-CoA structure, but becomes invisible in the hNaa60(1-199)/CoA structure, indicating displacement of the Phe 34 side-chain in the latter (Fig. 3A,B).	RESULTS
65	85	hNaa60(1-242)/Ac-CoA	complex_assembly	The electron density of Phe 34 side-chain is well defined in the hNaa60(1-242)/Ac-CoA structure, but becomes invisible in the hNaa60(1-199)/CoA structure, indicating displacement of the Phe 34 side-chain in the latter (Fig. 3A,B).	RESULTS
86	95	structure	evidence	The electron density of Phe 34 side-chain is well defined in the hNaa60(1-242)/Ac-CoA structure, but becomes invisible in the hNaa60(1-199)/CoA structure, indicating displacement of the Phe 34 side-chain in the latter (Fig. 3A,B).	RESULTS
126	143	hNaa60(1-199)/CoA	complex_assembly	The electron density of Phe 34 side-chain is well defined in the hNaa60(1-242)/Ac-CoA structure, but becomes invisible in the hNaa60(1-199)/CoA structure, indicating displacement of the Phe 34 side-chain in the latter (Fig. 3A,B).	RESULTS
144	153	structure	evidence	The electron density of Phe 34 side-chain is well defined in the hNaa60(1-242)/Ac-CoA structure, but becomes invisible in the hNaa60(1-199)/CoA structure, indicating displacement of the Phe 34 side-chain in the latter (Fig. 3A,B).	RESULTS
186	192	Phe 34	residue_name_number	The electron density of Phe 34 side-chain is well defined in the hNaa60(1-242)/Ac-CoA structure, but becomes invisible in the hNaa60(1-199)/CoA structure, indicating displacement of the Phe 34 side-chain in the latter (Fig. 3A,B).	RESULTS
18	26	malonate	chemical	A solvent-derived malonate molecule is found beside Phe 34 and the ethanethioate moiety of Ac-CoA in the high-resolution hNaa60(1-242)/Ac-CoA structure (Fig. 3A).	RESULTS
52	58	Phe 34	residue_name_number	A solvent-derived malonate molecule is found beside Phe 34 and the ethanethioate moiety of Ac-CoA in the high-resolution hNaa60(1-242)/Ac-CoA structure (Fig. 3A).	RESULTS
67	80	ethanethioate	chemical	A solvent-derived malonate molecule is found beside Phe 34 and the ethanethioate moiety of Ac-CoA in the high-resolution hNaa60(1-242)/Ac-CoA structure (Fig. 3A).	RESULTS
91	97	Ac-CoA	chemical	A solvent-derived malonate molecule is found beside Phe 34 and the ethanethioate moiety of Ac-CoA in the high-resolution hNaa60(1-242)/Ac-CoA structure (Fig. 3A).	RESULTS
121	141	hNaa60(1-242)/Ac-CoA	complex_assembly	A solvent-derived malonate molecule is found beside Phe 34 and the ethanethioate moiety of Ac-CoA in the high-resolution hNaa60(1-242)/Ac-CoA structure (Fig. 3A).	RESULTS
142	151	structure	evidence	A solvent-derived malonate molecule is found beside Phe 34 and the ethanethioate moiety of Ac-CoA in the high-resolution hNaa60(1-242)/Ac-CoA structure (Fig. 3A).	RESULTS
0	13	Superposition	experimental_method	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
22	31	structure	evidence	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
43	62	hNaa50p/CoA/peptide	complex_assembly	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
78	86	malonate	chemical	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
128	138	methionine	residue_name	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
156	163	peptide	chemical	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
176	182	Phe 34	residue_name_number	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
186	192	hNaa60	protein	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
210	216	Phe 27	residue_name_number	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
220	226	hNaa50	protein	Superposition of this structure on that of hNaa50p/CoA/peptide shows that the malonate molecule overlaps well on the N-terminal methionine of the substrate peptide and residue Phe 34 in hNaa60 overlaps well on Phe 27 in hNaa50 (Fig. 4A).	RESULTS
22	31	structure	evidence	Interestingly, in the structure of hNaa60(1-199)/CoA, the terminal thiol of CoA adopts alternative conformations.	RESULTS
35	52	hNaa60(1-199)/CoA	complex_assembly	Interestingly, in the structure of hNaa60(1-199)/CoA, the terminal thiol of CoA adopts alternative conformations.	RESULTS
76	79	CoA	chemical	Interestingly, in the structure of hNaa60(1-199)/CoA, the terminal thiol of CoA adopts alternative conformations.	RESULTS
33	38	amine	chemical	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
60	72	superimposed	experimental_method	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
73	91	hNaa50/CoA/peptide	complex_assembly	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
92	101	structure	evidence	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
128	141	ethanethioate	chemical	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
145	151	Ac-CoA	chemical	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
159	168	structure	evidence	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
172	192	hNaa60(1-242)/Ac-CoA	complex_assembly	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
223	233	α1-α2 loop	structure_element	One is to approach the substrate amine (as indicated by the superimposed hNaa50/CoA/peptide structure), similar to the terminal ethanethioate of Ac-CoA in the structure of hNaa60(1-242)/Ac-CoA; the other is to approach the α1-α2 loop and away from the substrate amine (Fig. 3B).	RESULTS
37	53	electron density	evidence	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
130	146	electron density	evidence	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
178	184	Phe 34	residue_name_number	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
189	195	solved	experimental_method	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
200	217	crystal structure	evidence	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
221	243	hNaa60(1-199) F34A/CoA	complex_assembly	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
249	258	structure	evidence	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
267	273	mutant	protein_state	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
295	312	hNaa60(1-199)/CoA	complex_assembly	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
347	363	electron density	evidence	To rule out the possibility that the electron density we define as the alternative conformation of the thiol terminus is residual electron density of the displaced side-chain of Phe 34, we solved the crystal structure of hNaa60(1-199) F34A/CoA. The structure of this mutant is highly similar to hNaa60(1-199)/CoA and there is essentially the same electron density corresponding to the alternative conformation of the thiol (Fig. 3C).	RESULTS
0	6	Phe 27	residue_name_number	Phe 27 in hNaa50p (equivalent to Phe 34 in hNaa60) has been implicated to facilitate the binding of N-terminal methionine of the substrate peptide through hydrophobic interaction.	RESULTS
10	17	hNaa50p	protein	Phe 27 in hNaa50p (equivalent to Phe 34 in hNaa60) has been implicated to facilitate the binding of N-terminal methionine of the substrate peptide through hydrophobic interaction.	RESULTS
33	39	Phe 34	residue_name_number	Phe 27 in hNaa50p (equivalent to Phe 34 in hNaa60) has been implicated to facilitate the binding of N-terminal methionine of the substrate peptide through hydrophobic interaction.	RESULTS
43	49	hNaa60	protein	Phe 27 in hNaa50p (equivalent to Phe 34 in hNaa60) has been implicated to facilitate the binding of N-terminal methionine of the substrate peptide through hydrophobic interaction.	RESULTS
111	121	methionine	residue_name	Phe 27 in hNaa50p (equivalent to Phe 34 in hNaa60) has been implicated to facilitate the binding of N-terminal methionine of the substrate peptide through hydrophobic interaction.	RESULTS
139	146	peptide	chemical	Phe 27 in hNaa50p (equivalent to Phe 34 in hNaa60) has been implicated to facilitate the binding of N-terminal methionine of the substrate peptide through hydrophobic interaction.	RESULTS
155	178	hydrophobic interaction	bond_interaction	Phe 27 in hNaa50p (equivalent to Phe 34 in hNaa60) has been implicated to facilitate the binding of N-terminal methionine of the substrate peptide through hydrophobic interaction.	RESULTS
16	29	hNaa60/Ac-CoA	complex_assembly	However, in the hNaa60/Ac-CoA structure, a hydrophilic malonate molecule is found at the same location where the N-terminal methionine should bind as is indicated by the superposition (Fig. 3A), suggesting that Phe 34 may accommodate binding of hydrophilic substrate, too.	RESULTS
30	39	structure	evidence	However, in the hNaa60/Ac-CoA structure, a hydrophilic malonate molecule is found at the same location where the N-terminal methionine should bind as is indicated by the superposition (Fig. 3A), suggesting that Phe 34 may accommodate binding of hydrophilic substrate, too.	RESULTS
55	63	malonate	chemical	However, in the hNaa60/Ac-CoA structure, a hydrophilic malonate molecule is found at the same location where the N-terminal methionine should bind as is indicated by the superposition (Fig. 3A), suggesting that Phe 34 may accommodate binding of hydrophilic substrate, too.	RESULTS
124	134	methionine	residue_name	However, in the hNaa60/Ac-CoA structure, a hydrophilic malonate molecule is found at the same location where the N-terminal methionine should bind as is indicated by the superposition (Fig. 3A), suggesting that Phe 34 may accommodate binding of hydrophilic substrate, too.	RESULTS
170	183	superposition	experimental_method	However, in the hNaa60/Ac-CoA structure, a hydrophilic malonate molecule is found at the same location where the N-terminal methionine should bind as is indicated by the superposition (Fig. 3A), suggesting that Phe 34 may accommodate binding of hydrophilic substrate, too.	RESULTS
211	217	Phe 34	residue_name_number	However, in the hNaa60/Ac-CoA structure, a hydrophilic malonate molecule is found at the same location where the N-terminal methionine should bind as is indicated by the superposition (Fig. 3A), suggesting that Phe 34 may accommodate binding of hydrophilic substrate, too.	RESULTS
25	31	Phe 34	residue_name_number	Moreover, orientation of Phe 34 side-chain seems to be co-related to positioning of the terminus of the co-enzyme and important for placing it at a location in close proximity to the substrate amine.	RESULTS
23	29	Phe 34	residue_name_number	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
97	100	Met	residue_name	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
113	119	mutate	experimental_method	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
128	131	Phe	residue_name	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
135	138	Ala	residue_name	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
205	211	Phe 34	residue_name_number	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
257	270	ethanethioate	chemical	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
281	287	Ac-CoA	chemical	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
293	301	mutation	experimental_method	We hypothesize that if Phe 34 only works to facilitate the binding of the hydrophobic N-terminal Met residue, to mutate it from Phe to Ala would not abolish the catalytic activity of this enzyme, while if Phe 34 also plays an essential role to position the ethanethioate moiety of Ac-CoA, the mutation would be expected to abrogate the activity of the enzyme.	RESULTS
12	31	enzyme kinetic data	evidence	Indeed, our enzyme kinetic data showed that hNaa60(1-199) F34A mutant showed no detectable activity (Fig. 5A).	RESULTS
44	57	hNaa60(1-199)	mutant	Indeed, our enzyme kinetic data showed that hNaa60(1-199) F34A mutant showed no detectable activity (Fig. 5A).	RESULTS
58	62	F34A	mutant	Indeed, our enzyme kinetic data showed that hNaa60(1-199) F34A mutant showed no detectable activity (Fig. 5A).	RESULTS
63	69	mutant	protein_state	Indeed, our enzyme kinetic data showed that hNaa60(1-199) F34A mutant showed no detectable activity (Fig. 5A).	RESULTS
109	115	mutant	protein_state	In order to rule out the possibility that the observed loss of activity may be related to bad folding of the mutant protein, we studied the circular dichroism (CD) spectrum of the protein (Fig. 5B) and determined its crystal structure (Fig. 3C).	RESULTS
140	158	circular dichroism	experimental_method	In order to rule out the possibility that the observed loss of activity may be related to bad folding of the mutant protein, we studied the circular dichroism (CD) spectrum of the protein (Fig. 5B) and determined its crystal structure (Fig. 3C).	RESULTS
160	162	CD	experimental_method	In order to rule out the possibility that the observed loss of activity may be related to bad folding of the mutant protein, we studied the circular dichroism (CD) spectrum of the protein (Fig. 5B) and determined its crystal structure (Fig. 3C).	RESULTS
164	172	spectrum	evidence	In order to rule out the possibility that the observed loss of activity may be related to bad folding of the mutant protein, we studied the circular dichroism (CD) spectrum of the protein (Fig. 5B) and determined its crystal structure (Fig. 3C).	RESULTS
217	234	crystal structure	evidence	In order to rule out the possibility that the observed loss of activity may be related to bad folding of the mutant protein, we studied the circular dichroism (CD) spectrum of the protein (Fig. 5B) and determined its crystal structure (Fig. 3C).	RESULTS
29	33	F34A	mutant	Both studies proved that the F34A mutant protein is well-folded.	RESULTS
34	40	mutant	protein_state	Both studies proved that the F34A mutant protein is well-folded.	RESULTS
52	63	well-folded	protein_state	Both studies proved that the F34A mutant protein is well-folded.	RESULTS
50	60	α1-α2 loop	structure_element	Many studies have addressed the crucial effect of α1-α2 loop on catalysis, showing that some residues located in this area are involved in the binding of substrates.	RESULTS
16	22	Phe 34	residue_name_number	We propose that Phe 34 may play a dual role both in interacting with the peptide substrate (recognition) and in positioning of the ethanethioate moiety of Ac-CoA to the right location to facilitate acetyl-transfer.	RESULTS
73	80	peptide	chemical	We propose that Phe 34 may play a dual role both in interacting with the peptide substrate (recognition) and in positioning of the ethanethioate moiety of Ac-CoA to the right location to facilitate acetyl-transfer.	RESULTS
131	144	ethanethioate	chemical	We propose that Phe 34 may play a dual role both in interacting with the peptide substrate (recognition) and in positioning of the ethanethioate moiety of Ac-CoA to the right location to facilitate acetyl-transfer.	RESULTS
155	161	Ac-CoA	chemical	We propose that Phe 34 may play a dual role both in interacting with the peptide substrate (recognition) and in positioning of the ethanethioate moiety of Ac-CoA to the right location to facilitate acetyl-transfer.	RESULTS
198	204	acetyl	chemical	We propose that Phe 34 may play a dual role both in interacting with the peptide substrate (recognition) and in positioning of the ethanethioate moiety of Ac-CoA to the right location to facilitate acetyl-transfer.	RESULTS
21	27	hNaa60	protein	Structural basis for hNaa60 substrate binding	RESULTS
70	76	hNaa60	protein	Several studies have demonstrated that the substrate specificities of hNaa60 and hNaa50 are highly overlapped.	RESULTS
81	87	hNaa50	protein	Several studies have demonstrated that the substrate specificities of hNaa60 and hNaa50 are highly overlapped.	RESULTS
4	13	structure	evidence	The structure of hNaa50p/CoA/peptide provides detailed information about the position of substrate N-terminal residues in the active site of hNaa50.	RESULTS
17	36	hNaa50p/CoA/peptide	complex_assembly	The structure of hNaa50p/CoA/peptide provides detailed information about the position of substrate N-terminal residues in the active site of hNaa50.	RESULTS
126	137	active site	site	The structure of hNaa50p/CoA/peptide provides detailed information about the position of substrate N-terminal residues in the active site of hNaa50.	RESULTS
141	147	hNaa50	protein	The structure of hNaa50p/CoA/peptide provides detailed information about the position of substrate N-terminal residues in the active site of hNaa50.	RESULTS
14	25	active site	site	Comparing the active site of hNaa60(1-242)/Ac-CoA with hNaa50p/CoA/peptide revealed that key catalytic and substrate binding residues are highly conserved in both proteins (Fig. 4A).	RESULTS
29	49	hNaa60(1-242)/Ac-CoA	complex_assembly	Comparing the active site of hNaa60(1-242)/Ac-CoA with hNaa50p/CoA/peptide revealed that key catalytic and substrate binding residues are highly conserved in both proteins (Fig. 4A).	RESULTS
55	74	hNaa50p/CoA/peptide	complex_assembly	Comparing the active site of hNaa60(1-242)/Ac-CoA with hNaa50p/CoA/peptide revealed that key catalytic and substrate binding residues are highly conserved in both proteins (Fig. 4A).	RESULTS
93	133	catalytic and substrate binding residues	site	Comparing the active site of hNaa60(1-242)/Ac-CoA with hNaa50p/CoA/peptide revealed that key catalytic and substrate binding residues are highly conserved in both proteins (Fig. 4A).	RESULTS
138	154	highly conserved	protein_state	Comparing the active site of hNaa60(1-242)/Ac-CoA with hNaa50p/CoA/peptide revealed that key catalytic and substrate binding residues are highly conserved in both proteins (Fig. 4A).	RESULTS
27	34	hNaa50p	protein	With respect to catalysis, hNaa50p has been shown to employ residues Tyr 73 and His 112 to abstract proton from the α-amino group from the substrate’s first residue through a well-ordered water.	RESULTS
69	75	Tyr 73	residue_name_number	With respect to catalysis, hNaa50p has been shown to employ residues Tyr 73 and His 112 to abstract proton from the α-amino group from the substrate’s first residue through a well-ordered water.	RESULTS
80	87	His 112	residue_name_number	With respect to catalysis, hNaa50p has been shown to employ residues Tyr 73 and His 112 to abstract proton from the α-amino group from the substrate’s first residue through a well-ordered water.	RESULTS
175	187	well-ordered	protein_state	With respect to catalysis, hNaa50p has been shown to employ residues Tyr 73 and His 112 to abstract proton from the α-amino group from the substrate’s first residue through a well-ordered water.	RESULTS
188	193	water	chemical	With respect to catalysis, hNaa50p has been shown to employ residues Tyr 73 and His 112 to abstract proton from the α-amino group from the substrate’s first residue through a well-ordered water.	RESULTS
2	14	well-ordered	protein_state	A well-ordered water was also found between Tyr 97 and His 138 in hNaa60 (1-199)/CoA and hNaa60 (1-242)/Ac-CoA (Fig. 4B).	RESULTS
15	20	water	chemical	A well-ordered water was also found between Tyr 97 and His 138 in hNaa60 (1-199)/CoA and hNaa60 (1-242)/Ac-CoA (Fig. 4B).	RESULTS
44	50	Tyr 97	residue_name_number	A well-ordered water was also found between Tyr 97 and His 138 in hNaa60 (1-199)/CoA and hNaa60 (1-242)/Ac-CoA (Fig. 4B).	RESULTS
55	62	His 138	residue_name_number	A well-ordered water was also found between Tyr 97 and His 138 in hNaa60 (1-199)/CoA and hNaa60 (1-242)/Ac-CoA (Fig. 4B).	RESULTS
66	84	hNaa60 (1-199)/CoA	complex_assembly	A well-ordered water was also found between Tyr 97 and His 138 in hNaa60 (1-199)/CoA and hNaa60 (1-242)/Ac-CoA (Fig. 4B).	RESULTS
89	110	hNaa60 (1-242)/Ac-CoA	complex_assembly	A well-ordered water was also found between Tyr 97 and His 138 in hNaa60 (1-199)/CoA and hNaa60 (1-242)/Ac-CoA (Fig. 4B).	RESULTS
29	35	Tyr 97	residue_name_number	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
40	47	His 138	residue_name_number	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
51	57	hNaa60	protein	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
72	79	mutated	experimental_method	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
98	105	alanine	residue_name	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
110	123	phenylalanine	residue_name	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
168	175	mutants	protein_state	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
188	202	kinetic assays	experimental_method	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
207	218	well-folded	protein_state	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
222	224	CD	experimental_method	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
225	232	spectra	evidence	To determine the function of Tyr 97 and His 138 in hNaa60 catalysis, we mutated these residues to alanine and phenylalanine, respectively, and confirmed that all these mutants used in our kinetic assays are well-folded by CD spectra (Fig. 5B).	RESULTS
45	53	SDS-PAGE	experimental_method	Purity of all proteins were also analyzed by SDS-PAGE (Figure S5).	RESULTS
24	31	mutants	protein_state	As show in Fig. 5A, the mutants Y97A, Y97F, H138A and H138F abolished the activity of hNaa60.	RESULTS
32	36	Y97A	mutant	As show in Fig. 5A, the mutants Y97A, Y97F, H138A and H138F abolished the activity of hNaa60.	RESULTS
38	42	Y97F	mutant	As show in Fig. 5A, the mutants Y97A, Y97F, H138A and H138F abolished the activity of hNaa60.	RESULTS
44	49	H138A	mutant	As show in Fig. 5A, the mutants Y97A, Y97F, H138A and H138F abolished the activity of hNaa60.	RESULTS
54	59	H138F	mutant	As show in Fig. 5A, the mutants Y97A, Y97F, H138A and H138F abolished the activity of hNaa60.	RESULTS
60	82	abolished the activity	protein_state	As show in Fig. 5A, the mutants Y97A, Y97F, H138A and H138F abolished the activity of hNaa60.	RESULTS
86	92	hNaa60	protein	As show in Fig. 5A, the mutants Y97A, Y97F, H138A and H138F abolished the activity of hNaa60.	RESULTS
16	22	mutate	experimental_method	In contrast, to mutate the nearby solvent exposed residue Glu 37 to Ala (E37A) has little impact on the activity of hNaa60 (Figs 4B and 5A).	RESULTS
34	49	solvent exposed	protein_state	In contrast, to mutate the nearby solvent exposed residue Glu 37 to Ala (E37A) has little impact on the activity of hNaa60 (Figs 4B and 5A).	RESULTS
58	64	Glu 37	residue_name_number	In contrast, to mutate the nearby solvent exposed residue Glu 37 to Ala (E37A) has little impact on the activity of hNaa60 (Figs 4B and 5A).	RESULTS
68	71	Ala	residue_name	In contrast, to mutate the nearby solvent exposed residue Glu 37 to Ala (E37A) has little impact on the activity of hNaa60 (Figs 4B and 5A).	RESULTS
73	77	E37A	mutant	In contrast, to mutate the nearby solvent exposed residue Glu 37 to Ala (E37A) has little impact on the activity of hNaa60 (Figs 4B and 5A).	RESULTS
116	122	hNaa60	protein	In contrast, to mutate the nearby solvent exposed residue Glu 37 to Ala (E37A) has little impact on the activity of hNaa60 (Figs 4B and 5A).	RESULTS
19	52	structural and functional studies	experimental_method	In conclusion, the structural and functional studies indicate that hNaa60 applies the same two base mechanism through Tyr 97, His 138 and a well-ordered water as was described for hNaa50.	RESULTS
67	73	hNaa60	protein	In conclusion, the structural and functional studies indicate that hNaa60 applies the same two base mechanism through Tyr 97, His 138 and a well-ordered water as was described for hNaa50.	RESULTS
118	124	Tyr 97	residue_name_number	In conclusion, the structural and functional studies indicate that hNaa60 applies the same two base mechanism through Tyr 97, His 138 and a well-ordered water as was described for hNaa50.	RESULTS
126	133	His 138	residue_name_number	In conclusion, the structural and functional studies indicate that hNaa60 applies the same two base mechanism through Tyr 97, His 138 and a well-ordered water as was described for hNaa50.	RESULTS
140	152	well-ordered	protein_state	In conclusion, the structural and functional studies indicate that hNaa60 applies the same two base mechanism through Tyr 97, His 138 and a well-ordered water as was described for hNaa50.	RESULTS
153	158	water	chemical	In conclusion, the structural and functional studies indicate that hNaa60 applies the same two base mechanism through Tyr 97, His 138 and a well-ordered water as was described for hNaa50.	RESULTS
180	186	hNaa50	protein	In conclusion, the structural and functional studies indicate that hNaa60 applies the same two base mechanism through Tyr 97, His 138 and a well-ordered water as was described for hNaa50.	RESULTS
4	12	malonate	chemical	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
38	58	hNaa60(1-242)/Ac-CoA	complex_assembly	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
59	76	crystal structure	evidence	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
132	138	hNaa60	protein	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
166	177	active site	site	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
206	209	Met	residue_name	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
227	234	peptide	chemical	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
242	255	superposition	experimental_method	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
265	284	hNaa50p/CoA/peptide	complex_assembly	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
285	294	structure	evidence	The malonate molecule observed in the hNaa60(1-242)/Ac-CoA crystal structure may be indicative of the substrate binding position of hNaa60 since it is located in the active site and overlaps the N-terminal Met of the substrate peptide in the superposition with the hNaa50p/CoA/peptide structure (Fig. 4A).	RESULTS
9	15	Tyr 38	residue_name_number	Residues Tyr 38, Asn 143 and Tyr 165 are located around the malonate and interact with it through direct hydrogen bonds or water bridge (Fig. 4C).	RESULTS
17	24	Asn 143	residue_name_number	Residues Tyr 38, Asn 143 and Tyr 165 are located around the malonate and interact with it through direct hydrogen bonds or water bridge (Fig. 4C).	RESULTS
29	36	Tyr 165	residue_name_number	Residues Tyr 38, Asn 143 and Tyr 165 are located around the malonate and interact with it through direct hydrogen bonds or water bridge (Fig. 4C).	RESULTS
60	68	malonate	chemical	Residues Tyr 38, Asn 143 and Tyr 165 are located around the malonate and interact with it through direct hydrogen bonds or water bridge (Fig. 4C).	RESULTS
105	119	hydrogen bonds	bond_interaction	Residues Tyr 38, Asn 143 and Tyr 165 are located around the malonate and interact with it through direct hydrogen bonds or water bridge (Fig. 4C).	RESULTS
123	135	water bridge	bond_interaction	Residues Tyr 38, Asn 143 and Tyr 165 are located around the malonate and interact with it through direct hydrogen bonds or water bridge (Fig. 4C).	RESULTS
9	17	malonate	chemical	Although malonate is negatively charged, which is different from that of lysine ε-amine or peptide N-terminal amine, similar hydrophilic interactions may take place when substrate amine presents in the same position, since Tyr 38, Asn 143 and Tyr 165 are not positively or negatively charged.	RESULTS
73	79	lysine	residue_name	Although malonate is negatively charged, which is different from that of lysine ε-amine or peptide N-terminal amine, similar hydrophilic interactions may take place when substrate amine presents in the same position, since Tyr 38, Asn 143 and Tyr 165 are not positively or negatively charged.	RESULTS
91	98	peptide	chemical	Although malonate is negatively charged, which is different from that of lysine ε-amine or peptide N-terminal amine, similar hydrophilic interactions may take place when substrate amine presents in the same position, since Tyr 38, Asn 143 and Tyr 165 are not positively or negatively charged.	RESULTS
125	149	hydrophilic interactions	bond_interaction	Although malonate is negatively charged, which is different from that of lysine ε-amine or peptide N-terminal amine, similar hydrophilic interactions may take place when substrate amine presents in the same position, since Tyr 38, Asn 143 and Tyr 165 are not positively or negatively charged.	RESULTS
223	229	Tyr 38	residue_name_number	Although malonate is negatively charged, which is different from that of lysine ε-amine or peptide N-terminal amine, similar hydrophilic interactions may take place when substrate amine presents in the same position, since Tyr 38, Asn 143 and Tyr 165 are not positively or negatively charged.	RESULTS
231	238	Asn 143	residue_name_number	Although malonate is negatively charged, which is different from that of lysine ε-amine or peptide N-terminal amine, similar hydrophilic interactions may take place when substrate amine presents in the same position, since Tyr 38, Asn 143 and Tyr 165 are not positively or negatively charged.	RESULTS
243	250	Tyr 165	residue_name_number	Although malonate is negatively charged, which is different from that of lysine ε-amine or peptide N-terminal amine, similar hydrophilic interactions may take place when substrate amine presents in the same position, since Tyr 38, Asn 143 and Tyr 165 are not positively or negatively charged.	RESULTS
57	61	Y38A	mutant	In agreement with this hypothesis, it was found that the Y38A, N143A and Y165A mutants all showed remarkably reduced activities as compared to WT, implying that these residues may be critical for substrate binding (Figs 4C and 5A).	RESULTS
63	68	N143A	mutant	In agreement with this hypothesis, it was found that the Y38A, N143A and Y165A mutants all showed remarkably reduced activities as compared to WT, implying that these residues may be critical for substrate binding (Figs 4C and 5A).	RESULTS
73	78	Y165A	mutant	In agreement with this hypothesis, it was found that the Y38A, N143A and Y165A mutants all showed remarkably reduced activities as compared to WT, implying that these residues may be critical for substrate binding (Figs 4C and 5A).	RESULTS
79	86	mutants	protein_state	In agreement with this hypothesis, it was found that the Y38A, N143A and Y165A mutants all showed remarkably reduced activities as compared to WT, implying that these residues may be critical for substrate binding (Figs 4C and 5A).	RESULTS
143	145	WT	protein_state	In agreement with this hypothesis, it was found that the Y38A, N143A and Y165A mutants all showed remarkably reduced activities as compared to WT, implying that these residues may be critical for substrate binding (Figs 4C and 5A).	RESULTS
4	14	β3-β4 loop	structure_element	The β3-β4 loop participates in the regulation of hNaa60-activity	RESULTS
49	55	hNaa60	protein	The β3-β4 loop participates in the regulation of hNaa60-activity	RESULTS
17	19	β3	structure_element	Residues between β3 and β4 of hNaa60 form a unique 20-residue long loop (residues 73–92) that is a short turn in many other NAT members (Fig. 1D).	RESULTS
24	26	β4	structure_element	Residues between β3 and β4 of hNaa60 form a unique 20-residue long loop (residues 73–92) that is a short turn in many other NAT members (Fig. 1D).	RESULTS
30	36	hNaa60	protein	Residues between β3 and β4 of hNaa60 form a unique 20-residue long loop (residues 73–92) that is a short turn in many other NAT members (Fig. 1D).	RESULTS
51	71	20-residue long loop	structure_element	Residues between β3 and β4 of hNaa60 form a unique 20-residue long loop (residues 73–92) that is a short turn in many other NAT members (Fig. 1D).	RESULTS
82	87	73–92	residue_range	Residues between β3 and β4 of hNaa60 form a unique 20-residue long loop (residues 73–92) that is a short turn in many other NAT members (Fig. 1D).	RESULTS
99	109	short turn	structure_element	Residues between β3 and β4 of hNaa60 form a unique 20-residue long loop (residues 73–92) that is a short turn in many other NAT members (Fig. 1D).	RESULTS
124	127	NAT	protein_type	Residues between β3 and β4 of hNaa60 form a unique 20-residue long loop (residues 73–92) that is a short turn in many other NAT members (Fig. 1D).	RESULTS
30	46	auto-acetylation	ptm	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
50	56	hNaa60	protein	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
56	59	K79	residue_name_number	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
92	98	hNaa60	protein	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
142	148	Lys 79	residue_name_number	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
152	162	acetylated	protein_state	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
170	188	crystal structures	evidence	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
216	232	electron density	evidence	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
236	242	Lys 79	residue_name_number	Previous study indicated that auto-acetylation of hNaa60K79 could influence the activity of hNaa60; however, we were not able to determine if Lys 79 is acetylated in our crystal structures due to poor quality of the electron density of Lys 79 side-chain.	RESULTS
18	35	mass spectrometry	experimental_method	We therefore used mass spectrometry to analyze if Lys 79 was acetylated in our bacterially purified proteins, and observed no modification on this residue (Figure S6).	RESULTS
50	56	Lys 79	residue_name_number	We therefore used mass spectrometry to analyze if Lys 79 was acetylated in our bacterially purified proteins, and observed no modification on this residue (Figure S6).	RESULTS
61	71	acetylated	protein_state	We therefore used mass spectrometry to analyze if Lys 79 was acetylated in our bacterially purified proteins, and observed no modification on this residue (Figure S6).	RESULTS
24	30	hNaa60	protein	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
30	33	K79	residue_name_number	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
34	50	auto-acetylation	ptm	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
79	83	K79R	mutant	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
88	92	K79Q	mutant	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
93	100	mutants	protein_state	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
117	130	un-acetylated	protein_state	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
135	145	acetylated	protein_state	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
154	160	Lys 79	residue_name_number	To assess the impact of hNaa60K79 auto-acetylation, we studied the kinetics of K79R and K79Q mutants which mimic the un-acetylated and acetylated form of Lys 79, respectively.	RESULTS
20	24	K79R	mutant	Interestingly, both K79R and K79Q mutants led to an increase in the catalytic activity of hNaa60, while K79A mutant led to modest decrease of the activity (Fig. 5A).	RESULTS
29	33	K79Q	mutant	Interestingly, both K79R and K79Q mutants led to an increase in the catalytic activity of hNaa60, while K79A mutant led to modest decrease of the activity (Fig. 5A).	RESULTS
34	41	mutants	protein_state	Interestingly, both K79R and K79Q mutants led to an increase in the catalytic activity of hNaa60, while K79A mutant led to modest decrease of the activity (Fig. 5A).	RESULTS
90	96	hNaa60	protein	Interestingly, both K79R and K79Q mutants led to an increase in the catalytic activity of hNaa60, while K79A mutant led to modest decrease of the activity (Fig. 5A).	RESULTS
104	108	K79A	mutant	Interestingly, both K79R and K79Q mutants led to an increase in the catalytic activity of hNaa60, while K79A mutant led to modest decrease of the activity (Fig. 5A).	RESULTS
109	115	mutant	protein_state	Interestingly, both K79R and K79Q mutants led to an increase in the catalytic activity of hNaa60, while K79A mutant led to modest decrease of the activity (Fig. 5A).	RESULTS
29	40	acetylation	ptm	These data indicate that the acetylation of Lys 79 is not required for optimal catalytic activity of hNaa60 in vitro.	RESULTS
44	50	Lys 79	residue_name_number	These data indicate that the acetylation of Lys 79 is not required for optimal catalytic activity of hNaa60 in vitro.	RESULTS
101	107	hNaa60	protein	These data indicate that the acetylation of Lys 79 is not required for optimal catalytic activity of hNaa60 in vitro.	RESULTS
21	31	β3-β4 loop	structure_element	It is noted that the β3-β4 loop of hNaa60 acts like a door leaf to partly cover the substrate-binding pathway.	RESULTS
35	41	hNaa60	protein	It is noted that the β3-β4 loop of hNaa60 acts like a door leaf to partly cover the substrate-binding pathway.	RESULTS
84	109	substrate-binding pathway	site	It is noted that the β3-β4 loop of hNaa60 acts like a door leaf to partly cover the substrate-binding pathway.	RESULTS
30	40	β3-β4 loop	structure_element	We hence hypothesize that the β3-β4 loop may interfere with the access of the peptide substrates and that the solvent-exposing Lys 79 may play a potential role to remove the door leaf when it hovers in solvent (Fig. 4D).	RESULTS
78	85	peptide	chemical	We hence hypothesize that the β3-β4 loop may interfere with the access of the peptide substrates and that the solvent-exposing Lys 79 may play a potential role to remove the door leaf when it hovers in solvent (Fig. 4D).	RESULTS
110	126	solvent-exposing	protein_state	We hence hypothesize that the β3-β4 loop may interfere with the access of the peptide substrates and that the solvent-exposing Lys 79 may play a potential role to remove the door leaf when it hovers in solvent (Fig. 4D).	RESULTS
127	133	Lys 79	residue_name_number	We hence hypothesize that the β3-β4 loop may interfere with the access of the peptide substrates and that the solvent-exposing Lys 79 may play a potential role to remove the door leaf when it hovers in solvent (Fig. 4D).	RESULTS
16	22	Glu 80	residue_name_number	Acidic residues Glu 80, Asp 81 and Asp 83 interact with His 138, His 159 and His 158 to maintain the conformation of the β3-β4 loop, thus contribute to control the substrate binding (Fig. 4D).	RESULTS
24	30	Asp 81	residue_name_number	Acidic residues Glu 80, Asp 81 and Asp 83 interact with His 138, His 159 and His 158 to maintain the conformation of the β3-β4 loop, thus contribute to control the substrate binding (Fig. 4D).	RESULTS
35	41	Asp 83	residue_name_number	Acidic residues Glu 80, Asp 81 and Asp 83 interact with His 138, His 159 and His 158 to maintain the conformation of the β3-β4 loop, thus contribute to control the substrate binding (Fig. 4D).	RESULTS
56	63	His 138	residue_name_number	Acidic residues Glu 80, Asp 81 and Asp 83 interact with His 138, His 159 and His 158 to maintain the conformation of the β3-β4 loop, thus contribute to control the substrate binding (Fig. 4D).	RESULTS
65	72	His 159	residue_name_number	Acidic residues Glu 80, Asp 81 and Asp 83 interact with His 138, His 159 and His 158 to maintain the conformation of the β3-β4 loop, thus contribute to control the substrate binding (Fig. 4D).	RESULTS
77	84	His 158	residue_name_number	Acidic residues Glu 80, Asp 81 and Asp 83 interact with His 138, His 159 and His 158 to maintain the conformation of the β3-β4 loop, thus contribute to control the substrate binding (Fig. 4D).	RESULTS
121	131	β3-β4 loop	structure_element	Acidic residues Glu 80, Asp 81 and Asp 83 interact with His 138, His 159 and His 158 to maintain the conformation of the β3-β4 loop, thus contribute to control the substrate binding (Fig. 4D).	RESULTS
30	37	mutated	experimental_method	To verify this hypothesis, we mutated Glu 80, Asp 81 and Asp 83 to Ala respectively.	RESULTS
38	44	Glu 80	residue_name_number	To verify this hypothesis, we mutated Glu 80, Asp 81 and Asp 83 to Ala respectively.	RESULTS
46	52	Asp 81	residue_name_number	To verify this hypothesis, we mutated Glu 80, Asp 81 and Asp 83 to Ala respectively.	RESULTS
57	63	Asp 83	residue_name_number	To verify this hypothesis, we mutated Glu 80, Asp 81 and Asp 83 to Ala respectively.	RESULTS
67	70	Ala	residue_name	To verify this hypothesis, we mutated Glu 80, Asp 81 and Asp 83 to Ala respectively.	RESULTS
29	33	E80A	mutant	In line with our hypothesis, E80A, D81A and D83A mutants exhibit at least 2-fold increase in hNaa60-activity (Fig. 5A).	RESULTS
35	39	D81A	mutant	In line with our hypothesis, E80A, D81A and D83A mutants exhibit at least 2-fold increase in hNaa60-activity (Fig. 5A).	RESULTS
44	48	D83A	mutant	In line with our hypothesis, E80A, D81A and D83A mutants exhibit at least 2-fold increase in hNaa60-activity (Fig. 5A).	RESULTS
49	56	mutants	protein_state	In line with our hypothesis, E80A, D81A and D83A mutants exhibit at least 2-fold increase in hNaa60-activity (Fig. 5A).	RESULTS
93	99	hNaa60	protein	In line with our hypothesis, E80A, D81A and D83A mutants exhibit at least 2-fold increase in hNaa60-activity (Fig. 5A).	RESULTS
19	28	structure	evidence	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
45	48	NAT	protein_type	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
54	69	S. solfataricus	species	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
86	111	10-residue long extension	structure_element	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
120	122	β3	structure_element	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
127	129	β4	structure_element	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
139	172	structure and biochemical studies	experimental_method	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
189	198	extension	structure_element	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
202	207	SsNat	protein	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
254	265	active site	site	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
281	286	SsNat	protein	Interestingly, the structure of an ancestral NAT from S. solfataricus also exhibits a 10-residue long extension between β3 and β4, and the structure and biochemical studies showed that the extension of SsNat has the ability to stabilize structure of the active site and potentiate SsNat-activity.	RESULTS
0	14	Nt-acetylation	ptm	Nt-acetylation, which is carried out by the NAT family acetyltransferases, is an ancient and essential modification of proteins.	DISCUSS
44	73	NAT family acetyltransferases	protein_type	Nt-acetylation, which is carried out by the NAT family acetyltransferases, is an ancient and essential modification of proteins.	DISCUSS
14	18	NATs	protein_type	Although many NATs are highly conserved from lower to higher eukaryotes and the substrate bias of them appears to be partially overlapped, there is a significant increase in the overall level of N-terminal acetylation from lower to higher eukaryotes.	DISCUSS
23	39	highly conserved	protein_state	Although many NATs are highly conserved from lower to higher eukaryotes and the substrate bias of them appears to be partially overlapped, there is a significant increase in the overall level of N-terminal acetylation from lower to higher eukaryotes.	DISCUSS
45	50	lower	taxonomy_domain	Although many NATs are highly conserved from lower to higher eukaryotes and the substrate bias of them appears to be partially overlapped, there is a significant increase in the overall level of N-terminal acetylation from lower to higher eukaryotes.	DISCUSS
54	71	higher eukaryotes	taxonomy_domain	Although many NATs are highly conserved from lower to higher eukaryotes and the substrate bias of them appears to be partially overlapped, there is a significant increase in the overall level of N-terminal acetylation from lower to higher eukaryotes.	DISCUSS
195	217	N-terminal acetylation	ptm	Although many NATs are highly conserved from lower to higher eukaryotes and the substrate bias of them appears to be partially overlapped, there is a significant increase in the overall level of N-terminal acetylation from lower to higher eukaryotes.	DISCUSS
223	228	lower	taxonomy_domain	Although many NATs are highly conserved from lower to higher eukaryotes and the substrate bias of them appears to be partially overlapped, there is a significant increase in the overall level of N-terminal acetylation from lower to higher eukaryotes.	DISCUSS
232	249	higher eukaryotes	taxonomy_domain	Although many NATs are highly conserved from lower to higher eukaryotes and the substrate bias of them appears to be partially overlapped, there is a significant increase in the overall level of N-terminal acetylation from lower to higher eukaryotes.	DISCUSS
50	55	Naa60	protein	In this study we provide structural insights into Naa60 found only in multicellular eukaryotes.	DISCUSS
70	94	multicellular eukaryotes	taxonomy_domain	In this study we provide structural insights into Naa60 found only in multicellular eukaryotes.	DISCUSS
18	24	hNaa60	protein	The N-terminus of hNaa60 harbors three hydrophobic residues (VVP) that makes it very difficult to express and purify the protein.	DISCUSS
61	64	VVP	structure_element	The N-terminus of hNaa60 harbors three hydrophobic residues (VVP) that makes it very difficult to express and purify the protein.	DISCUSS
27	36	replacing	experimental_method	This problem was solved by replacing residues 4–6 from VVP to EER that are found in Naa60 from Xenopus Laevis.	DISCUSS
46	49	4–6	residue_range	This problem was solved by replacing residues 4–6 from VVP to EER that are found in Naa60 from Xenopus Laevis.	DISCUSS
55	58	VVP	structure_element	This problem was solved by replacing residues 4–6 from VVP to EER that are found in Naa60 from Xenopus Laevis.	DISCUSS
62	65	EER	structure_element	This problem was solved by replacing residues 4–6 from VVP to EER that are found in Naa60 from Xenopus Laevis.	DISCUSS
84	89	Naa60	protein	This problem was solved by replacing residues 4–6 from VVP to EER that are found in Naa60 from Xenopus Laevis.	DISCUSS
95	109	Xenopus Laevis	species	This problem was solved by replacing residues 4–6 from VVP to EER that are found in Naa60 from Xenopus Laevis.	DISCUSS
6	11	Naa60	protein	Since Naa60 from human and from Xenopus Laevis are highly homologous (Fig. 1A), we speculate that these two proteins should have the same biological function.	DISCUSS
17	22	human	species	Since Naa60 from human and from Xenopus Laevis are highly homologous (Fig. 1A), we speculate that these two proteins should have the same biological function.	DISCUSS
32	46	Xenopus Laevis	species	Since Naa60 from human and from Xenopus Laevis are highly homologous (Fig. 1A), we speculate that these two proteins should have the same biological function.	DISCUSS
51	68	highly homologous	protein_state	Since Naa60 from human and from Xenopus Laevis are highly homologous (Fig. 1A), we speculate that these two proteins should have the same biological function.	DISCUSS
33	43	VVP to EER	mutant	Therefore it is deduced that the VVP to EER replacement on the N-terminus of hNaa60 may not interfere with its function.	DISCUSS
44	55	replacement	experimental_method	Therefore it is deduced that the VVP to EER replacement on the N-terminus of hNaa60 may not interfere with its function.	DISCUSS
77	83	hNaa60	protein	Therefore it is deduced that the VVP to EER replacement on the N-terminus of hNaa60 may not interfere with its function.	DISCUSS
16	22	hNaa60	protein	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
23	28	1-242	residue_range	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
30	39	structure	evidence	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
65	84	α-helical structure	structure_element	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
126	127	6	residue_number	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
131	138	proline	residue_name	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
161	174	hNaa60(1-199)	mutant	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
175	184	structure	evidence	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
219	241	semi-helical structure	structure_element	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
276	291	crystal packing	evidence	However, in the hNaa60(1-242) structure the N-terminus adopts an α-helical structure which will probably be kinked if residue 6 is proline (Fig. 1C), and in the hNaa60(1-199) structure the N-terminus adopts a different semi-helical structure (Fig. 1B) likely due to different crystal packing.	DISCUSS
47	56	wild-type	protein_state	Hence it is not clear if the N-terminal end of wild-type hNaa60 is an α-helix, and what roles the hydrophobic residues 4–6 play in structure and function of wild-type hNaa60.	DISCUSS
57	63	hNaa60	protein	Hence it is not clear if the N-terminal end of wild-type hNaa60 is an α-helix, and what roles the hydrophobic residues 4–6 play in structure and function of wild-type hNaa60.	DISCUSS
70	77	α-helix	structure_element	Hence it is not clear if the N-terminal end of wild-type hNaa60 is an α-helix, and what roles the hydrophobic residues 4–6 play in structure and function of wild-type hNaa60.	DISCUSS
119	122	4–6	residue_range	Hence it is not clear if the N-terminal end of wild-type hNaa60 is an α-helix, and what roles the hydrophobic residues 4–6 play in structure and function of wild-type hNaa60.	DISCUSS
157	166	wild-type	protein_state	Hence it is not clear if the N-terminal end of wild-type hNaa60 is an α-helix, and what roles the hydrophobic residues 4–6 play in structure and function of wild-type hNaa60.	DISCUSS
167	173	hNaa60	protein	Hence it is not clear if the N-terminal end of wild-type hNaa60 is an α-helix, and what roles the hydrophobic residues 4–6 play in structure and function of wild-type hNaa60.	DISCUSS
33	41	mutation	experimental_method	In addition to the three-residue mutation (VVP to EER), we also tried many other hNaa60 constructs, but only the full-length protein and the truncated variant 1-199 behaved well.	DISCUSS
43	46	VVP	structure_element	In addition to the three-residue mutation (VVP to EER), we also tried many other hNaa60 constructs, but only the full-length protein and the truncated variant 1-199 behaved well.	DISCUSS
50	53	EER	structure_element	In addition to the three-residue mutation (VVP to EER), we also tried many other hNaa60 constructs, but only the full-length protein and the truncated variant 1-199 behaved well.	DISCUSS
81	87	hNaa60	protein	In addition to the three-residue mutation (VVP to EER), we also tried many other hNaa60 constructs, but only the full-length protein and the truncated variant 1-199 behaved well.	DISCUSS
113	124	full-length	protein_state	In addition to the three-residue mutation (VVP to EER), we also tried many other hNaa60 constructs, but only the full-length protein and the truncated variant 1-199 behaved well.	DISCUSS
141	150	truncated	protein_state	In addition to the three-residue mutation (VVP to EER), we also tried many other hNaa60 constructs, but only the full-length protein and the truncated variant 1-199 behaved well.	DISCUSS
159	164	1-199	residue_range	In addition to the three-residue mutation (VVP to EER), we also tried many other hNaa60 constructs, but only the full-length protein and the truncated variant 1-199 behaved well.	DISCUSS
43	49	hNaa60	protein	The finding that the catalytic activity of hNaa60(1-242) is much lower than that of hNaa60(1-199) is intriguing.	DISCUSS
50	55	1-242	residue_range	The finding that the catalytic activity of hNaa60(1-242) is much lower than that of hNaa60(1-199) is intriguing.	DISCUSS
84	97	hNaa60(1-199)	mutant	The finding that the catalytic activity of hNaa60(1-242) is much lower than that of hNaa60(1-199) is intriguing.	DISCUSS
38	49	full-length	protein_state	We speculate that low activity of the full-length hNaa60 might be related to lack of Golgi localization of the enzyme in our in vitro studies or there remains some undiscovered auto-inhibitory regulation in the full-length protein.	DISCUSS
50	56	hNaa60	protein	We speculate that low activity of the full-length hNaa60 might be related to lack of Golgi localization of the enzyme in our in vitro studies or there remains some undiscovered auto-inhibitory regulation in the full-length protein.	DISCUSS
211	222	full-length	protein_state	We speculate that low activity of the full-length hNaa60 might be related to lack of Golgi localization of the enzyme in our in vitro studies or there remains some undiscovered auto-inhibitory regulation in the full-length protein.	DISCUSS
4	10	hNaa60	protein	The hNaa60 protein was proven to be localized on Golgi apparatus.	DISCUSS
41	62	transmembrane domains	structure_element	Aksnes and colleagues predicted putative transmembrane domains and two putative sites of S-palmitoylation, by bioinformatics means, to account for Golgi localization of the protein.	DISCUSS
89	105	S-palmitoylation	ptm	Aksnes and colleagues predicted putative transmembrane domains and two putative sites of S-palmitoylation, by bioinformatics means, to account for Golgi localization of the protein.	DISCUSS
10	17	mutated	experimental_method	They then mutated all five cysteine residues of hNaa60’s to serine, including the two putative S-palmitoylation sites.	DISCUSS
27	35	cysteine	residue_name	They then mutated all five cysteine residues of hNaa60’s to serine, including the two putative S-palmitoylation sites.	DISCUSS
48	54	hNaa60	protein	They then mutated all five cysteine residues of hNaa60’s to serine, including the two putative S-palmitoylation sites.	DISCUSS
60	66	serine	residue_name	They then mutated all five cysteine residues of hNaa60’s to serine, including the two putative S-palmitoylation sites.	DISCUSS
95	117	S-palmitoylation sites	site	They then mutated all five cysteine residues of hNaa60’s to serine, including the two putative S-palmitoylation sites.	DISCUSS
15	24	mutations	experimental_method	However, these mutations did not abolish Naa60 membrane localization, indicating that S-palmitoylation is unlikely to (solely) account for targeting hNaa60 on Golgi.	DISCUSS
41	46	Naa60	protein	However, these mutations did not abolish Naa60 membrane localization, indicating that S-palmitoylation is unlikely to (solely) account for targeting hNaa60 on Golgi.	DISCUSS
86	102	S-palmitoylation	ptm	However, these mutations did not abolish Naa60 membrane localization, indicating that S-palmitoylation is unlikely to (solely) account for targeting hNaa60 on Golgi.	DISCUSS
149	155	hNaa60	protein	However, these mutations did not abolish Naa60 membrane localization, indicating that S-palmitoylation is unlikely to (solely) account for targeting hNaa60 on Golgi.	DISCUSS
13	19	adding	experimental_method	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
29	36	217–242	residue_range	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
40	46	hNaa60	protein	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
68	75	217–236	residue_range	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
97	118	transmembrane domains	structure_element	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
141	145	eGFP	experimental_method	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
216	220	eGFP	experimental_method	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
221	234	hNaa60182-242	mutant	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
279	286	182–216	residue_range	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
327	333	hNaa60	protein	Furthermore, adding residues 217–242 of hNaa60 (containing residues 217–236, one of the putative transmembrane domains) to the C terminus of eGFP were not sufficient to localize the protein on Golgi apparatus, while eGFP-hNaa60182-242 was sufficient to, suggesting that residues 182–216 are important for Golgi localization of hNaa60.	DISCUSS
23	30	190–202	residue_range	We found that residues 190–202 formed an amphipathic helix with an array of hydrophobic residues located on one side.	DISCUSS
41	58	amphipathic helix	structure_element	We found that residues 190–202 formed an amphipathic helix with an array of hydrophobic residues located on one side.	DISCUSS
76	95	amphipathic helices	structure_element	This observation is reminiscent of the protein/membrane interaction through amphipathic helices in the cases of KalSec14, Atg3, PB1-F2 etc.	DISCUSS
112	120	KalSec14	protein	This observation is reminiscent of the protein/membrane interaction through amphipathic helices in the cases of KalSec14, Atg3, PB1-F2 etc.	DISCUSS
122	126	Atg3	protein	This observation is reminiscent of the protein/membrane interaction through amphipathic helices in the cases of KalSec14, Atg3, PB1-F2 etc.	DISCUSS
128	134	PB1-F2	protein	This observation is reminiscent of the protein/membrane interaction through amphipathic helices in the cases of KalSec14, Atg3, PB1-F2 etc.	DISCUSS
17	34	amphipathic helix	structure_element	In this model an amphipathic helix can immerse its hydrophobic side into the lipid bilayer through hydrophobic interactions.	DISCUSS
99	123	hydrophobic interactions	bond_interaction	In this model an amphipathic helix can immerse its hydrophobic side into the lipid bilayer through hydrophobic interactions.	DISCUSS
30	47	amphipathic helix	structure_element	Therefore we propose that the amphipathic helix α5 may contribute to Golgi localization of hNaa60.	DISCUSS
48	50	α5	structure_element	Therefore we propose that the amphipathic helix α5 may contribute to Golgi localization of hNaa60.	DISCUSS
91	97	hNaa60	protein	Therefore we propose that the amphipathic helix α5 may contribute to Golgi localization of hNaa60.	DISCUSS
43	46	NAT	protein_type	Previous studies indicated that members of NAT family are bi-functional NAT and KAT enzymes.	DISCUSS
72	75	NAT	protein_type	Previous studies indicated that members of NAT family are bi-functional NAT and KAT enzymes.	DISCUSS
80	83	KAT	protein_type	Previous studies indicated that members of NAT family are bi-functional NAT and KAT enzymes.	DISCUSS
15	25	structures	evidence	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
29	33	NATs	protein_type	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
81	94	β6-β7 hairpin	structure_element	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
95	99	loop	structure_element	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
111	115	NATs	protein_type	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
150	184	tunnel-like substrate-binding site	site	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
194	204	α1-α2 loop	structure_element	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
234	237	NAT	protein_type	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
246	249	KAT	protein_type	However, known structures of NATs do not well support this hypothesis, since the β6-β7 hairpin/loop of most of NATs is involved in the formation of a tunnel-like substrate-binding site with the α1-α2 loop, which would be good for the NAT but not KAT activity of the enzyme.	DISCUSS
0	15	Kinetic studies	experimental_method	Kinetic studies have been conducted to compare the NAT and KAT activity of hNaa50 in vitro, and indicate that the NAT activity of Naa50 is much higher than KAT activity.	DISCUSS
51	54	NAT	protein_type	Kinetic studies have been conducted to compare the NAT and KAT activity of hNaa50 in vitro, and indicate that the NAT activity of Naa50 is much higher than KAT activity.	DISCUSS
59	62	KAT	protein_type	Kinetic studies have been conducted to compare the NAT and KAT activity of hNaa50 in vitro, and indicate that the NAT activity of Naa50 is much higher than KAT activity.	DISCUSS
75	81	hNaa50	protein	Kinetic studies have been conducted to compare the NAT and KAT activity of hNaa50 in vitro, and indicate that the NAT activity of Naa50 is much higher than KAT activity.	DISCUSS
114	117	NAT	protein_type	Kinetic studies have been conducted to compare the NAT and KAT activity of hNaa50 in vitro, and indicate that the NAT activity of Naa50 is much higher than KAT activity.	DISCUSS
130	135	Naa50	protein	Kinetic studies have been conducted to compare the NAT and KAT activity of hNaa50 in vitro, and indicate that the NAT activity of Naa50 is much higher than KAT activity.	DISCUSS
156	159	KAT	protein_type	Kinetic studies have been conducted to compare the NAT and KAT activity of hNaa50 in vitro, and indicate that the NAT activity of Naa50 is much higher than KAT activity.	DISCUSS
56	59	KAT	protein_type	However, the substrate used in this study for assessing KAT activity was a small peptide which could not really mimic the 3D structure of a folded protein substrate in vivo.	DISCUSS
81	88	peptide	chemical	However, the substrate used in this study for assessing KAT activity was a small peptide which could not really mimic the 3D structure of a folded protein substrate in vivo.	DISCUSS
122	134	3D structure	evidence	However, the substrate used in this study for assessing KAT activity was a small peptide which could not really mimic the 3D structure of a folded protein substrate in vivo.	DISCUSS
140	146	folded	protein_state	However, the substrate used in this study for assessing KAT activity was a small peptide which could not really mimic the 3D structure of a folded protein substrate in vivo.	DISCUSS
4	21	mass spectrometry	experimental_method	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
22	26	data	evidence	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
60	71	acetylation	ptm	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
75	82	histone	protein_type	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
83	88	H3-H4	complex_assembly	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
89	97	tetramer	oligomeric_state	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
98	105	lysines	residue_name	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
115	137	N-terminal acetylation	ptm	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
142	160	lysine acetylation	ptm	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
168	175	peptide	chemical	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
188	202	activity assay	experimental_method	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
223	226	KAT	protein_type	Our mass spectrometry data indicated that there were robust acetylation of histone H3-H4 tetramer lysines and both N-terminal acetylation and lysine acetylation of the peptide used in the activity assay, thus confirmed the KAT activity of this enzyme in vitro.	DISCUSS
29	42	β7-β8 hairpin	structure_element	Conformational change of the β7-β8 hairpin (corresponding to the β6-β7 loop of other NATs) is noted in our structures (Figs 1D and 2C), which might provide an explanation to the NAT/KAT dual-activity in a structural biological view, but we were unable to rule out the possibility that the observed conformational change of this hairpin might be an artifact related to crystal packing or truncation of the C-terminal end of the protein.	DISCUSS
65	75	β6-β7 loop	structure_element	Conformational change of the β7-β8 hairpin (corresponding to the β6-β7 loop of other NATs) is noted in our structures (Figs 1D and 2C), which might provide an explanation to the NAT/KAT dual-activity in a structural biological view, but we were unable to rule out the possibility that the observed conformational change of this hairpin might be an artifact related to crystal packing or truncation of the C-terminal end of the protein.	DISCUSS
85	89	NATs	protein_type	Conformational change of the β7-β8 hairpin (corresponding to the β6-β7 loop of other NATs) is noted in our structures (Figs 1D and 2C), which might provide an explanation to the NAT/KAT dual-activity in a structural biological view, but we were unable to rule out the possibility that the observed conformational change of this hairpin might be an artifact related to crystal packing or truncation of the C-terminal end of the protein.	DISCUSS
107	117	structures	evidence	Conformational change of the β7-β8 hairpin (corresponding to the β6-β7 loop of other NATs) is noted in our structures (Figs 1D and 2C), which might provide an explanation to the NAT/KAT dual-activity in a structural biological view, but we were unable to rule out the possibility that the observed conformational change of this hairpin might be an artifact related to crystal packing or truncation of the C-terminal end of the protein.	DISCUSS
178	181	NAT	protein_type	Conformational change of the β7-β8 hairpin (corresponding to the β6-β7 loop of other NATs) is noted in our structures (Figs 1D and 2C), which might provide an explanation to the NAT/KAT dual-activity in a structural biological view, but we were unable to rule out the possibility that the observed conformational change of this hairpin might be an artifact related to crystal packing or truncation of the C-terminal end of the protein.	DISCUSS
182	185	KAT	protein_type	Conformational change of the β7-β8 hairpin (corresponding to the β6-β7 loop of other NATs) is noted in our structures (Figs 1D and 2C), which might provide an explanation to the NAT/KAT dual-activity in a structural biological view, but we were unable to rule out the possibility that the observed conformational change of this hairpin might be an artifact related to crystal packing or truncation of the C-terminal end of the protein.	DISCUSS
328	335	hairpin	structure_element	Conformational change of the β7-β8 hairpin (corresponding to the β6-β7 loop of other NATs) is noted in our structures (Figs 1D and 2C), which might provide an explanation to the NAT/KAT dual-activity in a structural biological view, but we were unable to rule out the possibility that the observed conformational change of this hairpin might be an artifact related to crystal packing or truncation of the C-terminal end of the protein.	DISCUSS
368	383	crystal packing	evidence	Conformational change of the β7-β8 hairpin (corresponding to the β6-β7 loop of other NATs) is noted in our structures (Figs 1D and 2C), which might provide an explanation to the NAT/KAT dual-activity in a structural biological view, but we were unable to rule out the possibility that the observed conformational change of this hairpin might be an artifact related to crystal packing or truncation of the C-terminal end of the protein.	DISCUSS
69	72	KAT	protein_type	Further studies are therefore needed to reveal the mechanism for the KAT activity of this enzyme.	DISCUSS
48	78	GCN5 histone acetyltransferase	protein_type	In early years, researchers found adjustment of GCN5 histone acetyltransferase structure when it binds CoA molecule.	DISCUSS
79	88	structure	evidence	In early years, researchers found adjustment of GCN5 histone acetyltransferase structure when it binds CoA molecule.	DISCUSS
103	106	CoA	chemical	In early years, researchers found adjustment of GCN5 histone acetyltransferase structure when it binds CoA molecule.	DISCUSS
4	13	complexed	protein_state	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
22	26	NatA	complex_assembly	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
80	90	α1-α2 loop	structure_element	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
158	180	substrate-binding site	site	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
208	213	Naa15	protein	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
229	234	Naa10	protein	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
240	249	catalytic	protein_state	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
250	257	subunit	structure_element	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
261	265	NatA	complex_assembly	The complexed form of NatA is more suitable for catalytic activation, since the α1-α2 loop undergoes a conformation change to participate in the formation of substrate-binding site when the auxiliary subunit Naa15 interacts with Naa10 (the catalytic subunit of NatA).	DISCUSS
7	16	structure	evidence	In the structure of hNaa50/CoA/peptide, Phe 27 in the α1-α2 loop appears to make hydrophobic interaction with the N-terminal Met of substrate peptide.	DISCUSS
20	38	hNaa50/CoA/peptide	complex_assembly	In the structure of hNaa50/CoA/peptide, Phe 27 in the α1-α2 loop appears to make hydrophobic interaction with the N-terminal Met of substrate peptide.	DISCUSS
40	46	Phe 27	residue_name_number	In the structure of hNaa50/CoA/peptide, Phe 27 in the α1-α2 loop appears to make hydrophobic interaction with the N-terminal Met of substrate peptide.	DISCUSS
54	64	α1-α2 loop	structure_element	In the structure of hNaa50/CoA/peptide, Phe 27 in the α1-α2 loop appears to make hydrophobic interaction with the N-terminal Met of substrate peptide.	DISCUSS
81	104	hydrophobic interaction	bond_interaction	In the structure of hNaa50/CoA/peptide, Phe 27 in the α1-α2 loop appears to make hydrophobic interaction with the N-terminal Met of substrate peptide.	DISCUSS
125	128	Met	residue_name	In the structure of hNaa50/CoA/peptide, Phe 27 in the α1-α2 loop appears to make hydrophobic interaction with the N-terminal Met of substrate peptide.	DISCUSS
142	149	peptide	chemical	In the structure of hNaa50/CoA/peptide, Phe 27 in the α1-α2 loop appears to make hydrophobic interaction with the N-terminal Met of substrate peptide.	DISCUSS
13	33	hNaa60(1-242)/Ac-CoA	complex_assembly	However, the hNaa60(1-242)/Ac-CoA crystal structure indicated that its counterpart in hNaa60, Phe 34, could also accommodate the binding of a hydrophilic malonate that occupied the substrate binding site although it maintained the same conformation as that observed in hNaa50.	DISCUSS
34	51	crystal structure	evidence	However, the hNaa60(1-242)/Ac-CoA crystal structure indicated that its counterpart in hNaa60, Phe 34, could also accommodate the binding of a hydrophilic malonate that occupied the substrate binding site although it maintained the same conformation as that observed in hNaa50.	DISCUSS
86	92	hNaa60	protein	However, the hNaa60(1-242)/Ac-CoA crystal structure indicated that its counterpart in hNaa60, Phe 34, could also accommodate the binding of a hydrophilic malonate that occupied the substrate binding site although it maintained the same conformation as that observed in hNaa50.	DISCUSS
94	100	Phe 34	residue_name_number	However, the hNaa60(1-242)/Ac-CoA crystal structure indicated that its counterpart in hNaa60, Phe 34, could also accommodate the binding of a hydrophilic malonate that occupied the substrate binding site although it maintained the same conformation as that observed in hNaa50.	DISCUSS
154	162	malonate	chemical	However, the hNaa60(1-242)/Ac-CoA crystal structure indicated that its counterpart in hNaa60, Phe 34, could also accommodate the binding of a hydrophilic malonate that occupied the substrate binding site although it maintained the same conformation as that observed in hNaa50.	DISCUSS
181	203	substrate binding site	site	However, the hNaa60(1-242)/Ac-CoA crystal structure indicated that its counterpart in hNaa60, Phe 34, could also accommodate the binding of a hydrophilic malonate that occupied the substrate binding site although it maintained the same conformation as that observed in hNaa50.	DISCUSS
269	275	hNaa50	protein	However, the hNaa60(1-242)/Ac-CoA crystal structure indicated that its counterpart in hNaa60, Phe 34, could also accommodate the binding of a hydrophilic malonate that occupied the substrate binding site although it maintained the same conformation as that observed in hNaa50.	DISCUSS
28	33	thiol	chemical	Interestingly, the terminal thiol of CoA adopted alternative conformations in the structure of hNaa60(1-199)/CoA. One was to approach the substrate amine; the other was to approach the α1-α2 loop and away from the substrate amine.	DISCUSS
37	40	CoA	chemical	Interestingly, the terminal thiol of CoA adopted alternative conformations in the structure of hNaa60(1-199)/CoA. One was to approach the substrate amine; the other was to approach the α1-α2 loop and away from the substrate amine.	DISCUSS
82	91	structure	evidence	Interestingly, the terminal thiol of CoA adopted alternative conformations in the structure of hNaa60(1-199)/CoA. One was to approach the substrate amine; the other was to approach the α1-α2 loop and away from the substrate amine.	DISCUSS
95	112	hNaa60(1-199)/CoA	complex_assembly	Interestingly, the terminal thiol of CoA adopted alternative conformations in the structure of hNaa60(1-199)/CoA. One was to approach the substrate amine; the other was to approach the α1-α2 loop and away from the substrate amine.	DISCUSS
185	195	α1-α2 loop	structure_element	Interestingly, the terminal thiol of CoA adopted alternative conformations in the structure of hNaa60(1-199)/CoA. One was to approach the substrate amine; the other was to approach the α1-α2 loop and away from the substrate amine.	DISCUSS
34	37	CoA	chemical	Same alternative conformations of CoA were observed in the hNaa60(1-199)(F34A) crystal structure, and our kinetic data showed that the F34A mutation abolished the activity of the enzyme.	DISCUSS
59	78	hNaa60(1-199)(F34A)	mutant	Same alternative conformations of CoA were observed in the hNaa60(1-199)(F34A) crystal structure, and our kinetic data showed that the F34A mutation abolished the activity of the enzyme.	DISCUSS
79	96	crystal structure	evidence	Same alternative conformations of CoA were observed in the hNaa60(1-199)(F34A) crystal structure, and our kinetic data showed that the F34A mutation abolished the activity of the enzyme.	DISCUSS
106	118	kinetic data	evidence	Same alternative conformations of CoA were observed in the hNaa60(1-199)(F34A) crystal structure, and our kinetic data showed that the F34A mutation abolished the activity of the enzyme.	DISCUSS
135	139	F34A	mutant	Same alternative conformations of CoA were observed in the hNaa60(1-199)(F34A) crystal structure, and our kinetic data showed that the F34A mutation abolished the activity of the enzyme.	DISCUSS
140	148	mutation	experimental_method	Same alternative conformations of CoA were observed in the hNaa60(1-199)(F34A) crystal structure, and our kinetic data showed that the F34A mutation abolished the activity of the enzyme.	DISCUSS
40	46	Phe 34	residue_name_number	Taken together, our data indicated that Phe 34 in hNaa60 may play a role in placing co-enzyme at the right location to facilitate the acetyl-transfer.	DISCUSS
50	56	hNaa60	protein	Taken together, our data indicated that Phe 34 in hNaa60 may play a role in placing co-enzyme at the right location to facilitate the acetyl-transfer.	DISCUSS
134	140	acetyl	chemical	Taken together, our data indicated that Phe 34 in hNaa60 may play a role in placing co-enzyme at the right location to facilitate the acetyl-transfer.	DISCUSS
59	65	Phe 34	residue_name_number	However, these data did not rule out that possibility that Phe 34 may coordinate the binding of the N-terminal Met through hydrophobic interaction as was proposed by previous studies.	DISCUSS
111	114	Met	residue_name	However, these data did not rule out that possibility that Phe 34 may coordinate the binding of the N-terminal Met through hydrophobic interaction as was proposed by previous studies.	DISCUSS
123	146	hydrophobic interaction	bond_interaction	However, these data did not rule out that possibility that Phe 34 may coordinate the binding of the N-terminal Met through hydrophobic interaction as was proposed by previous studies.	DISCUSS
28	34	hNaa60	protein	Furthermore, we showed that hNaa60 adopts the classical two base mechanism to catalyze acetyl-transfer.	DISCUSS
87	93	acetyl	chemical	Furthermore, we showed that hNaa60 adopts the classical two base mechanism to catalyze acetyl-transfer.	DISCUSS
35	41	hNaa60	protein	Although sequence identity between hNaa60 and hNaa50 is low, key residues in the active site of both enzymes are highly conserved.	DISCUSS
46	52	hNaa50	protein	Although sequence identity between hNaa60 and hNaa50 is low, key residues in the active site of both enzymes are highly conserved.	DISCUSS
81	92	active site	site	Although sequence identity between hNaa60 and hNaa50 is low, key residues in the active site of both enzymes are highly conserved.	DISCUSS
113	129	highly conserved	protein_state	Although sequence identity between hNaa60 and hNaa50 is low, key residues in the active site of both enzymes are highly conserved.	DISCUSS
82	88	hNaa60	protein	This can reasonably explain the high overlapping substrates specificities between hNaa60 and hNaa50.	DISCUSS
93	99	hNaa50	protein	This can reasonably explain the high overlapping substrates specificities between hNaa60 and hNaa50.	DISCUSS
30	36	hNaa60	protein	Another structural feature of hNaa60 that distinguishes it from other NATs is the β3-β4 long loop which appears to inhibit the catalytic activity of hNaa60.	DISCUSS
70	74	NATs	protein_type	Another structural feature of hNaa60 that distinguishes it from other NATs is the β3-β4 long loop which appears to inhibit the catalytic activity of hNaa60.	DISCUSS
82	97	β3-β4 long loop	structure_element	Another structural feature of hNaa60 that distinguishes it from other NATs is the β3-β4 long loop which appears to inhibit the catalytic activity of hNaa60.	DISCUSS
149	155	hNaa60	protein	Another structural feature of hNaa60 that distinguishes it from other NATs is the β3-β4 long loop which appears to inhibit the catalytic activity of hNaa60.	DISCUSS
14	18	loop	structure_element	However, this loop also seems to stabilize the whole hNaa60 structure, because deletion mutations of this region led to protein precipitation and aggregation (Figure S7).	DISCUSS
53	59	hNaa60	protein	However, this loop also seems to stabilize the whole hNaa60 structure, because deletion mutations of this region led to protein precipitation and aggregation (Figure S7).	DISCUSS
60	69	structure	evidence	However, this loop also seems to stabilize the whole hNaa60 structure, because deletion mutations of this region led to protein precipitation and aggregation (Figure S7).	DISCUSS
79	97	deletion mutations	experimental_method	However, this loop also seems to stabilize the whole hNaa60 structure, because deletion mutations of this region led to protein precipitation and aggregation (Figure S7).	DISCUSS
36	52	auto-acetylation	ptm	A previous study suggested that the auto-acetylation of Lys 79 was important for hNaa60-activity, whereas the point mutation K79R did not decrease the activity of hNaa60 in our study.	DISCUSS
56	62	Lys 79	residue_name_number	A previous study suggested that the auto-acetylation of Lys 79 was important for hNaa60-activity, whereas the point mutation K79R did not decrease the activity of hNaa60 in our study.	DISCUSS
81	87	hNaa60	protein	A previous study suggested that the auto-acetylation of Lys 79 was important for hNaa60-activity, whereas the point mutation K79R did not decrease the activity of hNaa60 in our study.	DISCUSS
110	124	point mutation	experimental_method	A previous study suggested that the auto-acetylation of Lys 79 was important for hNaa60-activity, whereas the point mutation K79R did not decrease the activity of hNaa60 in our study.	DISCUSS
125	129	K79R	mutant	A previous study suggested that the auto-acetylation of Lys 79 was important for hNaa60-activity, whereas the point mutation K79R did not decrease the activity of hNaa60 in our study.	DISCUSS
163	169	hNaa60	protein	A previous study suggested that the auto-acetylation of Lys 79 was important for hNaa60-activity, whereas the point mutation K79R did not decrease the activity of hNaa60 in our study.	DISCUSS
14	30	electron density	evidence	Meanwhile, no electron density of acetyl group was found on Lys 79 in our structures and mass spectrometry analysis.	DISCUSS
34	40	acetyl	chemical	Meanwhile, no electron density of acetyl group was found on Lys 79 in our structures and mass spectrometry analysis.	DISCUSS
60	66	Lys 79	residue_name_number	Meanwhile, no electron density of acetyl group was found on Lys 79 in our structures and mass spectrometry analysis.	DISCUSS
74	84	structures	evidence	Meanwhile, no electron density of acetyl group was found on Lys 79 in our structures and mass spectrometry analysis.	DISCUSS
89	106	mass spectrometry	experimental_method	Meanwhile, no electron density of acetyl group was found on Lys 79 in our structures and mass spectrometry analysis.	DISCUSS
27	43	auto-acetylation	ptm	Hence, it appears that the auto-acetylation of hNaa60 is not an essential modification for its activity for the protein we used here.	DISCUSS
47	53	hNaa60	protein	Hence, it appears that the auto-acetylation of hNaa60 is not an essential modification for its activity for the protein we used here.	DISCUSS
22	26	K79R	mutant	As for the reason why K79R in Yang’s previous studies reduced the activity of the enzyme, but in our studies it didn’t, we suspect that the stability of this mutant may play some role.	DISCUSS
158	164	mutant	protein_state	As for the reason why K79R in Yang’s previous studies reduced the activity of the enzyme, but in our studies it didn’t, we suspect that the stability of this mutant may play some role.	DISCUSS
0	4	K79R	mutant	K79R is less stable than the wild-type enzyme as was judged by its poorer gel-filtration behavior and tendency to precipitate.	DISCUSS
13	19	stable	protein_state	K79R is less stable than the wild-type enzyme as was judged by its poorer gel-filtration behavior and tendency to precipitate.	DISCUSS
29	38	wild-type	protein_state	K79R is less stable than the wild-type enzyme as was judged by its poorer gel-filtration behavior and tendency to precipitate.	DISCUSS
74	88	gel-filtration	experimental_method	K79R is less stable than the wild-type enzyme as was judged by its poorer gel-filtration behavior and tendency to precipitate.	DISCUSS
151	165	kinetic assays	experimental_method	In our studies we have paid special attention and carefully handled this protein to ensure that we did get enough of the protein in good condition for kinetic assays.	DISCUSS
107	113	hNaa60	protein	The intracellular environment is more complicated than our in vitro assay and the substrate specificity of hNaa60 most focuses on transmembrane proteins.	DISCUSS
24	30	hNaa60	protein	The interaction between hNaa60 and its substrates may involve the protein-membrane interaction which would further increase the complexity.	DISCUSS
23	32	structure	evidence	It is not clear if the structure of hNaa60 is different in vivo or if other potential partner proteins may help to regulate its activity.	DISCUSS
36	42	hNaa60	protein	It is not clear if the structure of hNaa60 is different in vivo or if other potential partner proteins may help to regulate its activity.	DISCUSS
129	132	NAT	protein_type	Nevertheless, our study may be an inspiration for further studies on the functions and regulation of this youngest member of the NAT family.	DISCUSS
8	17	structure	evidence	Overall structure of Naa60.	FIG
21	26	Naa60	protein	Overall structure of Naa60.	FIG
4	22	Sequence alignment	experimental_method	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
26	31	Naa60	protein	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
33	37	NatF	complex_assembly	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
39	43	HAT4	protein	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
78	90	Homo sapiens	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
92	96	Homo	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
99	108	Bos mutus	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
110	113	Bos	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
116	127	Salmo salar	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
129	134	Salmo	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
140	147	Xenopus	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
149	157	Silurana	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
159	169	tropicalis	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
171	178	Xenopus	species	(A) Sequence alignment of Naa60 (NatF, HAT4) from different species including Homo sapiens (Homo), Bos mutus (Bos), Salmo salar (Salmo) and Xenopus (Silurana) tropicalis (Xenopus).	FIG
0	9	Alignment	experimental_method	Alignment was generated using NPS@ and ESPript.3.0 (http://espript.ibcp.fr/ESPript/ESPript/).	FIG
9	12	4–6	residue_range	Residues 4–6 are highlighted in red box.	FIG
8	17	structure	evidence	(B) The structure of hNaa60(1-199)/CoA complex is shown as a yellow cartoon model.	FIG
21	38	hNaa60(1-199)/CoA	complex_assembly	(B) The structure of hNaa60(1-199)/CoA complex is shown as a yellow cartoon model.	FIG
4	7	CoA	chemical	The CoA molecule is shown as sticks. (C) The structure of hNaa60(1-242)/Ac-CoA complex is presented as a cartoon model in cyan.	FIG
45	54	structure	evidence	The CoA molecule is shown as sticks. (C) The structure of hNaa60(1-242)/Ac-CoA complex is presented as a cartoon model in cyan.	FIG
58	78	hNaa60(1-242)/Ac-CoA	complex_assembly	The CoA molecule is shown as sticks. (C) The structure of hNaa60(1-242)/Ac-CoA complex is presented as a cartoon model in cyan.	FIG
4	10	Ac-CoA	chemical	The Ac-CoA and malonate molecules are shown as cyan and purple sticks, respectively.	FIG
15	23	malonate	chemical	The Ac-CoA and malonate molecules are shown as cyan and purple sticks, respectively.	FIG
51	53	α0	structure_element	The secondary structures are labeled starting with α0. (D) Superposition of hNaa60(1-242) (cyan), hNaa60(1-199) (yellow) and hNaa50 (pink, PDB 3TFY).	FIG
59	72	Superposition	experimental_method	The secondary structures are labeled starting with α0. (D) Superposition of hNaa60(1-242) (cyan), hNaa60(1-199) (yellow) and hNaa50 (pink, PDB 3TFY).	FIG
76	82	hNaa60	protein	The secondary structures are labeled starting with α0. (D) Superposition of hNaa60(1-242) (cyan), hNaa60(1-199) (yellow) and hNaa50 (pink, PDB 3TFY).	FIG
83	88	1-242	residue_range	The secondary structures are labeled starting with α0. (D) Superposition of hNaa60(1-242) (cyan), hNaa60(1-199) (yellow) and hNaa50 (pink, PDB 3TFY).	FIG
98	111	hNaa60(1-199)	mutant	The secondary structures are labeled starting with α0. (D) Superposition of hNaa60(1-242) (cyan), hNaa60(1-199) (yellow) and hNaa50 (pink, PDB 3TFY).	FIG
125	131	hNaa50	protein	The secondary structures are labeled starting with α0. (D) Superposition of hNaa60(1-242) (cyan), hNaa60(1-199) (yellow) and hNaa50 (pink, PDB 3TFY).	FIG
4	10	Ac-CoA	chemical	The Ac-CoA of hNaa60(1-242)/Ac-CoA complex is represented as cyan sticks.	FIG
14	34	hNaa60(1-242)/Ac-CoA	complex_assembly	The Ac-CoA of hNaa60(1-242)/Ac-CoA complex is represented as cyan sticks.	FIG
0	14	Amphipathicity	protein_state	Amphipathicity of the α5 helix and alternative conformations of the β7-β8 hairpin.	FIG
22	30	α5 helix	structure_element	Amphipathicity of the α5 helix and alternative conformations of the β7-β8 hairpin.	FIG
68	81	β7-β8 hairpin	structure_element	Amphipathicity of the α5 helix and alternative conformations of the β7-β8 hairpin.	FIG
8	16	α5 helix	structure_element	(A) The α5 helix of hNaa60(1-242) in one asymmetric unit (slate) interacts with another hNaa60 molecule in a neighboring asymmetric unit (cyan).	FIG
20	26	hNaa60	protein	(A) The α5 helix of hNaa60(1-242) in one asymmetric unit (slate) interacts with another hNaa60 molecule in a neighboring asymmetric unit (cyan).	FIG
27	32	1-242	residue_range	(A) The α5 helix of hNaa60(1-242) in one asymmetric unit (slate) interacts with another hNaa60 molecule in a neighboring asymmetric unit (cyan).	FIG
88	94	hNaa60	protein	(A) The α5 helix of hNaa60(1-242) in one asymmetric unit (slate) interacts with another hNaa60 molecule in a neighboring asymmetric unit (cyan).	FIG
39	47	α5 helix	structure_element	Side-chains of hydrophobic residues on α5 helix and the neighboring molecule participating in the interaction are shown as yellow and green sticks, respectively. (B) The α5 helix of hNaa60(1-199) in one asymmetric unit (yellow) interacts with another hNaa60 molecule in the neighboring asymmetric units (green).	FIG
170	178	α5 helix	structure_element	Side-chains of hydrophobic residues on α5 helix and the neighboring molecule participating in the interaction are shown as yellow and green sticks, respectively. (B) The α5 helix of hNaa60(1-199) in one asymmetric unit (yellow) interacts with another hNaa60 molecule in the neighboring asymmetric units (green).	FIG
182	195	hNaa60(1-199)	mutant	Side-chains of hydrophobic residues on α5 helix and the neighboring molecule participating in the interaction are shown as yellow and green sticks, respectively. (B) The α5 helix of hNaa60(1-199) in one asymmetric unit (yellow) interacts with another hNaa60 molecule in the neighboring asymmetric units (green).	FIG
251	257	hNaa60	protein	Side-chains of hydrophobic residues on α5 helix and the neighboring molecule participating in the interaction are shown as yellow and green sticks, respectively. (B) The α5 helix of hNaa60(1-199) in one asymmetric unit (yellow) interacts with another hNaa60 molecule in the neighboring asymmetric units (green).	FIG
39	47	α5 helix	structure_element	Side-chains of hydrophobic residues on α5 helix and the neighboring molecule (green) participating in the interaction are shown as yellow and green sticks, respectively.	FIG
62	70	α5 helix	structure_element	The third molecule (pink) does not directly interact with the α5 helix.	FIG
4	17	Superposition	experimental_method	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
21	34	hNaa60(1-199)	mutant	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
48	54	hNaa60	protein	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
55	60	1-242	residue_range	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
106	119	β7-β8 hairpin	structure_element	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
133	143	structures	evidence	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
151	164	Superposition	experimental_method	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
168	173	Hat1p	protein	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
174	176	H4	protein_type	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
210	216	hNaa60	protein	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
217	222	1-242	residue_range	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
237	250	hNaa60(1-199)	mutant	(C) Superposition of hNaa60(1-199) (yellow) and hNaa60(1-242) (cyan) showing conformational change of the β7-β8 hairpin in these two structures. (D,E) Superposition of Hat1p/H4 (gray, drawn from PDB 4PSW) with hNaa60(1-242) (cyan, D) or hNaa60(1-199) (yellow, E).	FIG
4	11	histone	protein_type	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
12	14	H4	protein_type	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
15	22	peptide	chemical	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
26	29	KAT	protein_type	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
41	49	bound to	protein_state	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
50	55	Hat1p	protein	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
92	99	peptide	chemical	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
100	108	bound to	protein_state	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
109	115	hNaa50	protein	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
119	122	NAT	protein_type	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
175	185	Nt-peptide	chemical	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
193	206	superimposing	experimental_method	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
207	213	hNaa50	protein	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
239	245	hNaa60	protein	The histone H4 peptide (a KAT substrate) bound to Hat1p is shown in purple (D,E), while the peptide bound to hNaa50 (a NAT substrate, drawn from PDB 3TFY) is shown in orange (Nt-peptide) after superimposing hNaa50 (not shown in figure) on hNaa60 (D).	FIG
19	22	NAT	protein_type	The α-amine of the NAT substrate and ε-amine of the KAT substrate (along with the lysine side-chain) subject to acetylation are shown as sticks.	FIG
52	55	KAT	protein_type	The α-amine of the NAT substrate and ε-amine of the KAT substrate (along with the lysine side-chain) subject to acetylation are shown as sticks.	FIG
82	88	lysine	residue_name	The α-amine of the NAT substrate and ε-amine of the KAT substrate (along with the lysine side-chain) subject to acetylation are shown as sticks.	FIG
112	123	acetylation	ptm	The α-amine of the NAT substrate and ε-amine of the KAT substrate (along with the lysine side-chain) subject to acetylation are shown as sticks.	FIG
0	20	Electron density map	evidence	Electron density map of the active site.	FIG
28	39	active site	site	Electron density map of the active site.	FIG
4	15	2Fo-Fc maps	evidence	The 2Fo-Fc maps contoured at 1.0σ are shown for hNaa60(1-242)/Ac-CoA (A), hNaa60(1-199)/CoA (B) and hNaa60(1-199) F34A/CoA (C).	FIG
48	68	hNaa60(1-242)/Ac-CoA	complex_assembly	The 2Fo-Fc maps contoured at 1.0σ are shown for hNaa60(1-242)/Ac-CoA (A), hNaa60(1-199)/CoA (B) and hNaa60(1-199) F34A/CoA (C).	FIG
74	91	hNaa60(1-199)/CoA	complex_assembly	The 2Fo-Fc maps contoured at 1.0σ are shown for hNaa60(1-242)/Ac-CoA (A), hNaa60(1-199)/CoA (B) and hNaa60(1-199) F34A/CoA (C).	FIG
100	122	hNaa60(1-199) F34A/CoA	complex_assembly	The 2Fo-Fc maps contoured at 1.0σ are shown for hNaa60(1-242)/Ac-CoA (A), hNaa60(1-199)/CoA (B) and hNaa60(1-199) F34A/CoA (C).	FIG
13	43	substrate peptide binding site	site	The putative substrate peptide binding site is indicated by the peptide (shown as pink sticks) from the hNaa50/CoA/peptide complex structure after superimposing hNaa50 on the hNaa60 structures determined in this study.	FIG
64	71	peptide	chemical	The putative substrate peptide binding site is indicated by the peptide (shown as pink sticks) from the hNaa50/CoA/peptide complex structure after superimposing hNaa50 on the hNaa60 structures determined in this study.	FIG
104	122	hNaa50/CoA/peptide	complex_assembly	The putative substrate peptide binding site is indicated by the peptide (shown as pink sticks) from the hNaa50/CoA/peptide complex structure after superimposing hNaa50 on the hNaa60 structures determined in this study.	FIG
131	140	structure	evidence	The putative substrate peptide binding site is indicated by the peptide (shown as pink sticks) from the hNaa50/CoA/peptide complex structure after superimposing hNaa50 on the hNaa60 structures determined in this study.	FIG
147	160	superimposing	experimental_method	The putative substrate peptide binding site is indicated by the peptide (shown as pink sticks) from the hNaa50/CoA/peptide complex structure after superimposing hNaa50 on the hNaa60 structures determined in this study.	FIG
161	167	hNaa50	protein	The putative substrate peptide binding site is indicated by the peptide (shown as pink sticks) from the hNaa50/CoA/peptide complex structure after superimposing hNaa50 on the hNaa60 structures determined in this study.	FIG
175	181	hNaa60	protein	The putative substrate peptide binding site is indicated by the peptide (shown as pink sticks) from the hNaa50/CoA/peptide complex structure after superimposing hNaa50 on the hNaa60 structures determined in this study.	FIG
182	192	structures	evidence	The putative substrate peptide binding site is indicated by the peptide (shown as pink sticks) from the hNaa50/CoA/peptide complex structure after superimposing hNaa50 on the hNaa60 structures determined in this study.	FIG
45	54	first Met	residue_name_number	The black arrow indicates the α-amine of the first Met (M1) (all panels).	FIG
56	58	M1	residue_name_number	The black arrow indicates the α-amine of the first Met (M1) (all panels).	FIG
31	37	acetyl	chemical	The purple arrow indicates the acetyl moiety of Ac-CoA (A).	FIG
48	54	Ac-CoA	chemical	The purple arrow indicates the acetyl moiety of Ac-CoA (A).	FIG
95	101	Phe 34	residue_name_number	The red arrow indicates the alternative conformation of the thiol moiety of the co-enzyme when Phe 34 side-chain is displaced (B) or mutated to Ala (C).	FIG
133	140	mutated	experimental_method	The red arrow indicates the alternative conformation of the thiol moiety of the co-enzyme when Phe 34 side-chain is displaced (B) or mutated to Ala (C).	FIG
144	147	Ala	residue_name	The red arrow indicates the alternative conformation of the thiol moiety of the co-enzyme when Phe 34 side-chain is displaced (B) or mutated to Ala (C).	FIG
21	27	hNaa60	protein	Structural basis for hNaa60 catalytic activity.	FIG
4	17	Superposition	experimental_method	(A) Superposition of hNaa60 active site (cyan) on that of hNaa50 (pink, PDB 3TFY).	FIG
21	27	hNaa60	protein	(A) Superposition of hNaa60 active site (cyan) on that of hNaa50 (pink, PDB 3TFY).	FIG
28	39	active site	site	(A) Superposition of hNaa60 active site (cyan) on that of hNaa50 (pink, PDB 3TFY).	FIG
58	64	hNaa50	protein	(A) Superposition of hNaa60 active site (cyan) on that of hNaa50 (pink, PDB 3TFY).	FIG
19	59	catalytic and substrate-binding residues	site	Side-chains of key catalytic and substrate-binding residues are highlighted as sticks.	FIG
4	12	malonate	chemical	The malonate molecule in the hNaa60(1-242)/Ac-CoA structure and the peptide in the hNaa50/CoA/peptide structure are shown as purple and yellow sticks respectively. (B) A close view of the active site of hNaa60.	FIG
29	49	hNaa60(1-242)/Ac-CoA	complex_assembly	The malonate molecule in the hNaa60(1-242)/Ac-CoA structure and the peptide in the hNaa50/CoA/peptide structure are shown as purple and yellow sticks respectively. (B) A close view of the active site of hNaa60.	FIG
50	59	structure	evidence	The malonate molecule in the hNaa60(1-242)/Ac-CoA structure and the peptide in the hNaa50/CoA/peptide structure are shown as purple and yellow sticks respectively. (B) A close view of the active site of hNaa60.	FIG
68	75	peptide	chemical	The malonate molecule in the hNaa60(1-242)/Ac-CoA structure and the peptide in the hNaa50/CoA/peptide structure are shown as purple and yellow sticks respectively. (B) A close view of the active site of hNaa60.	FIG
83	101	hNaa50/CoA/peptide	complex_assembly	The malonate molecule in the hNaa60(1-242)/Ac-CoA structure and the peptide in the hNaa50/CoA/peptide structure are shown as purple and yellow sticks respectively. (B) A close view of the active site of hNaa60.	FIG
102	111	structure	evidence	The malonate molecule in the hNaa60(1-242)/Ac-CoA structure and the peptide in the hNaa50/CoA/peptide structure are shown as purple and yellow sticks respectively. (B) A close view of the active site of hNaa60.	FIG
188	199	active site	site	The malonate molecule in the hNaa60(1-242)/Ac-CoA structure and the peptide in the hNaa50/CoA/peptide structure are shown as purple and yellow sticks respectively. (B) A close view of the active site of hNaa60.	FIG
203	209	hNaa60	protein	The malonate molecule in the hNaa60(1-242)/Ac-CoA structure and the peptide in the hNaa50/CoA/peptide structure are shown as purple and yellow sticks respectively. (B) A close view of the active site of hNaa60.	FIG
9	15	Glu 37	residue_name_number	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
17	23	Tyr 97	residue_name_number	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
28	35	His 138	residue_name_number	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
39	45	hNaa60	protein	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
81	87	Tyr 73	residue_name_number	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
92	99	His 112	residue_name_number	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
104	110	hNaa50	protein	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
171	177	Glu 24	residue_name_number	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
179	185	His 72	residue_name_number	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
190	197	His 111	residue_name_number	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
202	211	complexed	protein_state	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
219	226	hNaa10p	protein	Residues Glu 37, Tyr 97 and His 138 in hNaa60 (cyan) and corresponding residues (Tyr 73 and His 112) in hNaa50 (pink) as well as the side-chain of corresponding residues (Glu 24, His 72 and His 111) in complexed formed hNaa10p (warmpink) are highlighted as sticks.	FIG
4	9	water	chemical	The water molecules participating in catalysis in the hNaa60 and hNaa50 structures are showed as green and red spheres, separately. (C) The interaction between the malonate molecule and surrounding residues observed in the hNaa60(1-242)/Ac-CoA structure.	FIG
54	60	hNaa60	protein	The water molecules participating in catalysis in the hNaa60 and hNaa50 structures are showed as green and red spheres, separately. (C) The interaction between the malonate molecule and surrounding residues observed in the hNaa60(1-242)/Ac-CoA structure.	FIG
65	71	hNaa50	protein	The water molecules participating in catalysis in the hNaa60 and hNaa50 structures are showed as green and red spheres, separately. (C) The interaction between the malonate molecule and surrounding residues observed in the hNaa60(1-242)/Ac-CoA structure.	FIG
72	82	structures	evidence	The water molecules participating in catalysis in the hNaa60 and hNaa50 structures are showed as green and red spheres, separately. (C) The interaction between the malonate molecule and surrounding residues observed in the hNaa60(1-242)/Ac-CoA structure.	FIG
164	172	malonate	chemical	The water molecules participating in catalysis in the hNaa60 and hNaa50 structures are showed as green and red spheres, separately. (C) The interaction between the malonate molecule and surrounding residues observed in the hNaa60(1-242)/Ac-CoA structure.	FIG
223	243	hNaa60(1-242)/Ac-CoA	complex_assembly	The water molecules participating in catalysis in the hNaa60 and hNaa50 structures are showed as green and red spheres, separately. (C) The interaction between the malonate molecule and surrounding residues observed in the hNaa60(1-242)/Ac-CoA structure.	FIG
244	253	structure	evidence	The water molecules participating in catalysis in the hNaa60 and hNaa50 structures are showed as green and red spheres, separately. (C) The interaction between the malonate molecule and surrounding residues observed in the hNaa60(1-242)/Ac-CoA structure.	FIG
37	51	hydrogen bonds	bond_interaction	The yellow dotted lines indicate the hydrogen bonds. (D) A zoomed view of β3-β4 loop of hNaa60.	FIG
74	84	β3-β4 loop	structure_element	The yellow dotted lines indicate the hydrogen bonds. (D) A zoomed view of β3-β4 loop of hNaa60.	FIG
88	94	hNaa60	protein	The yellow dotted lines indicate the hydrogen bonds. (D) A zoomed view of β3-β4 loop of hNaa60.	FIG
47	55	malonate	chemical	Key residues discussed in the text (cyan), the malonate (purple) and Ac-CoA (gray) are shown as sticks.	FIG
69	75	Ac-CoA	chemical	Key residues discussed in the text (cyan), the malonate (purple) and Ac-CoA (gray) are shown as sticks.	FIG
37	49	salt bridges	bond_interaction	The yellow dotted lines indicate the salt bridges.	FIG
22	28	hNaa60	protein	Catalytic activity of hNaa60 and mutant proteins.	FIG
33	39	mutant	protein_state	Catalytic activity of hNaa60 and mutant proteins.	FIG
4	24	Catalytic efficiency	evidence	(A) Catalytic efficiency (shown as kcat/Km values) of hNaa60 (1-199) WT and mutants.	FIG
35	39	kcat	evidence	(A) Catalytic efficiency (shown as kcat/Km values) of hNaa60 (1-199) WT and mutants.	FIG
40	42	Km	evidence	(A) Catalytic efficiency (shown as kcat/Km values) of hNaa60 (1-199) WT and mutants.	FIG
54	68	hNaa60 (1-199)	mutant	(A) Catalytic efficiency (shown as kcat/Km values) of hNaa60 (1-199) WT and mutants.	FIG
69	71	WT	protein_state	(A) Catalytic efficiency (shown as kcat/Km values) of hNaa60 (1-199) WT and mutants.	FIG
76	83	mutants	protein_state	(A) Catalytic efficiency (shown as kcat/Km values) of hNaa60 (1-199) WT and mutants.	FIG
4	6	CD	experimental_method	(B) CD spectra of wild-type and mutant proteins from 250 nm to 190 nm.	FIG
7	14	spectra	evidence	(B) CD spectra of wild-type and mutant proteins from 250 nm to 190 nm.	FIG
18	27	wild-type	protein_state	(B) CD spectra of wild-type and mutant proteins from 250 nm to 190 nm.	FIG
32	38	mutant	protein_state	(B) CD spectra of wild-type and mutant proteins from 250 nm to 190 nm.	FIG
93	97	TCEP	chemical	The sample concentration was 4.5 μM in 20 mM Tris, pH 8.0, 150 mM NaCl, 1% glycerol and 1 mM TCEP at room temperature.	FIG
0	41	Data collection and refinement statistics	evidence	Data collection and refinement statistics.	TABLE
21	41	hNaa60(1-242)/Ac-CoA	complex_assembly	"Structure and PDB ID	hNaa60(1-242)/Ac-CoA 5HGZ	hNaa60(1-199)/CoA 5HH0	hNaa60(1-199)F34A/CoA 5HH1	 	Data collection*	 	 Space group	P212121	P21212	P21212	 	Cell dimensions	 	 a, b, c (Å)	53.3, 57.4, 68.8	67.8, 73.8, 43.2	66.7, 74.0, 43.5	 	 α,β,γ (°)	90.0, 90.0, 90.0	90.0, 90.0, 90.0	90.0, 90.0, 90.0	 	Resolution (Å)	50–1.38 (1.42–1.38)	50–1.60 (1.66–1.60)	50–1.80 (1.86–1.80)	 	Rp.i.m.(%)**	3.0 (34.4)	2.1 (32.5)	2.6 (47.8)	 	I/σ	21.5 (2.0)	31.8 (2.0)	28.0 (2.4)	 	Completeness (%)	99.8 (99.1)	99.6 (98.5)	99.9 (99.7)	 	Redundancy	6.9 (5.0)	6.9 (6.2)	6.3 (5.9)	 	Refinement	 	 Resolution (Å)	25.81–1.38	33.55–1.60	43.52–1.80	 	 No. reflections	43660	28588	20490	 	 Rwork/Rfree	0.182/0.192	0.181/0.184	0.189/0.209	 	No. atoms	 	 Protein	1717	1576	1566	 	 Ligand/ion	116	96	96	 	 Water	289	258	168	 	B-factors	 	 Protein	23.8	32.0	37.4	 	 Ligand/ion	22.2	34.6	43.7	 	 Water	35.1	46.4	49.1	 	R.m.s."	TABLE
47	64	hNaa60(1-199)/CoA	complex_assembly	"Structure and PDB ID	hNaa60(1-242)/Ac-CoA 5HGZ	hNaa60(1-199)/CoA 5HH0	hNaa60(1-199)F34A/CoA 5HH1	 	Data collection*	 	 Space group	P212121	P21212	P21212	 	Cell dimensions	 	 a, b, c (Å)	53.3, 57.4, 68.8	67.8, 73.8, 43.2	66.7, 74.0, 43.5	 	 α,β,γ (°)	90.0, 90.0, 90.0	90.0, 90.0, 90.0	90.0, 90.0, 90.0	 	Resolution (Å)	50–1.38 (1.42–1.38)	50–1.60 (1.66–1.60)	50–1.80 (1.86–1.80)	 	Rp.i.m.(%)**	3.0 (34.4)	2.1 (32.5)	2.6 (47.8)	 	I/σ	21.5 (2.0)	31.8 (2.0)	28.0 (2.4)	 	Completeness (%)	99.8 (99.1)	99.6 (98.5)	99.9 (99.7)	 	Redundancy	6.9 (5.0)	6.9 (6.2)	6.3 (5.9)	 	Refinement	 	 Resolution (Å)	25.81–1.38	33.55–1.60	43.52–1.80	 	 No. reflections	43660	28588	20490	 	 Rwork/Rfree	0.182/0.192	0.181/0.184	0.189/0.209	 	No. atoms	 	 Protein	1717	1576	1566	 	 Ligand/ion	116	96	96	 	 Water	289	258	168	 	B-factors	 	 Protein	23.8	32.0	37.4	 	 Ligand/ion	22.2	34.6	43.7	 	 Water	35.1	46.4	49.1	 	R.m.s."	TABLE
70	91	hNaa60(1-199)F34A/CoA	complex_assembly	"Structure and PDB ID	hNaa60(1-242)/Ac-CoA 5HGZ	hNaa60(1-199)/CoA 5HH0	hNaa60(1-199)F34A/CoA 5HH1	 	Data collection*	 	 Space group	P212121	P21212	P21212	 	Cell dimensions	 	 a, b, c (Å)	53.3, 57.4, 68.8	67.8, 73.8, 43.2	66.7, 74.0, 43.5	 	 α,β,γ (°)	90.0, 90.0, 90.0	90.0, 90.0, 90.0	90.0, 90.0, 90.0	 	Resolution (Å)	50–1.38 (1.42–1.38)	50–1.60 (1.66–1.60)	50–1.80 (1.86–1.80)	 	Rp.i.m.(%)**	3.0 (34.4)	2.1 (32.5)	2.6 (47.8)	 	I/σ	21.5 (2.0)	31.8 (2.0)	28.0 (2.4)	 	Completeness (%)	99.8 (99.1)	99.6 (98.5)	99.9 (99.7)	 	Redundancy	6.9 (5.0)	6.9 (6.2)	6.3 (5.9)	 	Refinement	 	 Resolution (Å)	25.81–1.38	33.55–1.60	43.52–1.80	 	 No. reflections	43660	28588	20490	 	 Rwork/Rfree	0.182/0.192	0.181/0.184	0.189/0.209	 	No. atoms	 	 Protein	1717	1576	1566	 	 Ligand/ion	116	96	96	 	 Water	289	258	168	 	B-factors	 	 Protein	23.8	32.0	37.4	 	 Ligand/ion	22.2	34.6	43.7	 	 Water	35.1	46.4	49.1	 	R.m.s."	TABLE
780	785	Water	chemical	"Structure and PDB ID	hNaa60(1-242)/Ac-CoA 5HGZ	hNaa60(1-199)/CoA 5HH0	hNaa60(1-199)F34A/CoA 5HH1	 	Data collection*	 	 Space group	P212121	P21212	P21212	 	Cell dimensions	 	 a, b, c (Å)	53.3, 57.4, 68.8	67.8, 73.8, 43.2	66.7, 74.0, 43.5	 	 α,β,γ (°)	90.0, 90.0, 90.0	90.0, 90.0, 90.0	90.0, 90.0, 90.0	 	Resolution (Å)	50–1.38 (1.42–1.38)	50–1.60 (1.66–1.60)	50–1.80 (1.86–1.80)	 	Rp.i.m.(%)**	3.0 (34.4)	2.1 (32.5)	2.6 (47.8)	 	I/σ	21.5 (2.0)	31.8 (2.0)	28.0 (2.4)	 	Completeness (%)	99.8 (99.1)	99.6 (98.5)	99.9 (99.7)	 	Redundancy	6.9 (5.0)	6.9 (6.2)	6.3 (5.9)	 	Refinement	 	 Resolution (Å)	25.81–1.38	33.55–1.60	43.52–1.80	 	 No. reflections	43660	28588	20490	 	 Rwork/Rfree	0.182/0.192	0.181/0.184	0.189/0.209	 	No. atoms	 	 Protein	1717	1576	1566	 	 Ligand/ion	116	96	96	 	 Water	289	258	168	 	B-factors	 	 Protein	23.8	32.0	37.4	 	 Ligand/ion	22.2	34.6	43.7	 	 Water	35.1	46.4	49.1	 	R.m.s."	TABLE
868	873	Water	chemical	"Structure and PDB ID	hNaa60(1-242)/Ac-CoA 5HGZ	hNaa60(1-199)/CoA 5HH0	hNaa60(1-199)F34A/CoA 5HH1	 	Data collection*	 	 Space group	P212121	P21212	P21212	 	Cell dimensions	 	 a, b, c (Å)	53.3, 57.4, 68.8	67.8, 73.8, 43.2	66.7, 74.0, 43.5	 	 α,β,γ (°)	90.0, 90.0, 90.0	90.0, 90.0, 90.0	90.0, 90.0, 90.0	 	Resolution (Å)	50–1.38 (1.42–1.38)	50–1.60 (1.66–1.60)	50–1.80 (1.86–1.80)	 	Rp.i.m.(%)**	3.0 (34.4)	2.1 (32.5)	2.6 (47.8)	 	I/σ	21.5 (2.0)	31.8 (2.0)	28.0 (2.4)	 	Completeness (%)	99.8 (99.1)	99.6 (98.5)	99.9 (99.7)	 	Redundancy	6.9 (5.0)	6.9 (6.2)	6.3 (5.9)	 	Refinement	 	 Resolution (Å)	25.81–1.38	33.55–1.60	43.52–1.80	 	 No. reflections	43660	28588	20490	 	 Rwork/Rfree	0.182/0.192	0.181/0.184	0.189/0.209	 	No. atoms	 	 Protein	1717	1576	1566	 	 Ligand/ion	116	96	96	 	 Water	289	258	168	 	B-factors	 	 Protein	23.8	32.0	37.4	 	 Ligand/ion	22.2	34.6	43.7	 	 Water	35.1	46.4	49.1	 	R.m.s."	TABLE
4	11	crystal	evidence	One crystal was used for each data set.	TABLE
36	44	R factor	evidence	**Rp.i.m., a redundancy-independent R factor was used to evaluate the diffraction data quality as was proposed by Evans.	TABLE
70	86	diffraction data	evidence	**Rp.i.m., a redundancy-independent R factor was used to evaluate the diffraction data quality as was proposed by Evans.	TABLE