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Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Mar 1;69(Pt 3):243-7. doi: 10.1107/S1744309113002352. Epub 2013 Feb 22.

Structure of Pseudomonas aeruginosa inosine 5'-monophosphate dehydrogenase.

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  • 1Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland.

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 (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.

KEYWORDS:

Pseudomonas aeruginosa; antimicrobial drug targets; inosine 5′-monophosphate dehydrogenase

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