Structure of Pseudomonas aeruginosa inosine 5'-monophosphate dehydrogenase.
Inosine 5'-monophosphate dehydrogenase (IMPDH) represents a potential antimicrobial drug target. The crystal structure of recombinant Pseudomonas aeruginosa IMPDH has been determined to a resolution of 2.25 Å. The structure is a homotetramer of subunits dominated by a (β/α)8-barrel fold, consistent with other known structures of IMPDH. Also in common with previous work, the cystathionine β-synthase domains, residues 92-204, are not present in the model owing to disorder. However, unlike the majority of available structures, clearly defined electron density exists for a loop that creates part of the active site. This loop, composed of residues 297-315, links α8 and β9 and carries the catalytic Cys304. P. aeruginosa IMPDH shares a high level of sequence identity with bacterial and protozoan homologues, with residues involved in binding substrate and the NAD+ cofactor being conserved. Specific differences that have been proven to contribute to selectivity against the human enzyme in a study of Cryptosporidium parvum IMPDH are also conserved, highlighting the potential value of IMPDH as a drug target.
['Rao|Vincenzo A|VA|', 'Shepherd|Sharon M|SM|', 'Owen|Richard|R|', 'Hunter|William N|WN|']
D000595:Amino Acid Sequence D001426:Bacterial Proteins D020134:Catalytic Domain D017124:Conserved Sequence D016785:Cryptosporidium parvum D018360:Crystallography, X-Ray D003545:Cysteine D004926:Escherichia coli D007168:IMP Dehydrogenase D008958:Models, Molecular D008969:Molecular Sequence Data D055503:Protein Multimerization D017433:Protein Structure, Secondary D017434:Protein Structure, Tertiary D011550:Pseudomonas aeruginosa D016415:Sequence Alignment D017386:Sequence Homology, Amino Acid D013045:Species Specificity
Pseudomonas aeruginosa antimicrobial drug targets inosine 5′-monophosphate dehydrogenase