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Publication Abstract from PubMed

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 A. The structure is a homotetramer of subunits dominated by a (beta/alpha)8-barrel fold, consistent with other known structures of IMPDH. Also in common with previous work, the cystathionine beta-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 alpha8 and beta9 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.

Structure of Pseudomonas aeruginosa inosine 5'-monophosphate dehydrogenase.,Rao VA, Shepherd SM, Owen R, Hunter WN Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Mar 1;69(Pt 3):243-7. doi:, 10.1107/S1744309113002352. Epub 2013 Feb 22. PMID:23519796^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.