Open AccessStructure of Pseudomonas aeruginosa inosine 5′‐monophosphate dehydrogenase
Author(s) -
Rao Vincenzo A.,
Shepherd Sharon M.,
Owen Richard,
Hunter William N.
Publication year - 2013
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309113002352
Subject(s) - homotetramer , cofactor , biochemistry , imp dehydrogenase , nad+ kinase , pseudomonas aeruginosa , active site , enzyme , biology , dehydrogenase , chemistry , nucleotide , inosine , stereochemistry , bacteria , protein subunit , gene , genetics , medicine , transplantation , mycophenolic acid , surgery
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.