2gkl
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Crystal structure of the zinc carbapenemase CPHA in complex with the inhibitor pyridine-2,4-dicarboxylate
OverviewOverview
Various inhibitors of metallo-beta-lactamases have been reported, however, none are effective for all subgroups. Those that have been found to, inhibit the enzymes of subclass B2 (catalytically active with one zinc), either contain a thiol (and show less inhibition towards this subgroup, than towards the dizinc members of B1 and B3) or are inactivators behaving, as substrates for the dizinc family members. The present work reveals that, certain pyridine carboxylates are competitive inhibitors of CphA, a, subclass B2 enzyme. X-ray crystallographic analyses demonstrate that, pyridine-2,4-dicarboxylic acid chelates the zinc ion in a bidentate manner, within the active site. Salts of these compounds are already available and, undergoing biomedical testing for various non-related purposes., Pyridine-carboxylates appear useful templates for the development of more, complex, selective, non-toxic inhibitors of the subclass B2, metallo-beta-lactamases.
About this StructureAbout this Structure
2GKL is a Single protein structure of sequence from Aeromonas hydrophila with ZN, PD2 and GOL as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
ReferenceReference
Competitive Inhibitors of the CphA Metallo-{beta}-Lactamase from Aeromonas hydrophila., Horsfall LE, Garau G, Lienard BM, Dideberg O, Schofield CJ, Frere JM, Galleni M, Antimicrob Agents Chemother. 2007 Feb 16;. PMID:17307979
Page seeded by OCA on Wed Nov 21 11:15:09 2007