Structure of Pseudomonas aeruginosa inosine 5'-monophosphate dehydrogenase.

ABSTRACT: 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 (?/?)8-barrel fold, consistent with other known structures of IMPDH. Also in common with previous work, the cystathionine ?-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 ?8 and ?9 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.

SUBMITTER: Rao VA 

PROVIDER: S-EPMC3606566 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature