Influence of the conformations of αA-crystallin peptides on the isomerization rates of aspartic acid residues.
The isomerization rate of aspartic acid (Asp) residue is known to be affected by the three-dimensional structures of peptides and proteins. Although the isomerized Asp residues were experimentally observed, structural features which affect the isomerization cannot be elucidated sufficiently because of protein denaturation and aggregation. In this study, molecular dynamics (MD) simulations were conducted on three αA-crystallin peptides (T6, T10, and T18), each containing a single Asp residue with different isomerization rate (T18 > T6 > T10) to clarify the structural factors of Asp isomerization tendency. For MD trajectories, distances between side-chain carboxyl carbon of Asp and main-chain amide nitrogen of (n + 1) residue (Cγ-N distances), root mean square fluctuations (RMSFs), and polar surface areas for main-chain amide nitrogen of (n + 1) residues (PSAN) were calculated, because these structural features are considered to relate to the formations of cyclic imide intermediates. RMSFs and PSAN are indexes of peptide backbone flexibilities and solvent exposure of the amide nitrogen, respectively. The average Cγ-N distances of T10 was longer than those of the other two peptides. In addition, the peptide containing Asp residue with a higher isomerization rate showed higher flexibility of the peptide backbone around the Asp residue. PSAN for amide nitrogen in T18 were much larger than those of other two peptides. The computational results suggest that Asp-residue isomerization rates are affected by these factors.
['Nakayoshi|Tomoki|T|', 'Kato|Koichi|K|', 'Kurimoto|Eiji|E|', 'Oda|Akifumi|A|']
D000595:Amino Acid Sequence D001224:Aspartic Acid D008958:Models, Molecular D008968:Molecular Conformation D015394:Molecular Structure D010455:Peptides D013237:Stereoisomerism D038202:alpha-Crystallin A Chain
Isomerization Molecular dynamics simulation Peptide conformation Succinimide d-aspartic acid