2gkl
Crystal structure of the zinc carbapenemase CPHA in complex with the inhibitor pyridine-2,4-dicarboxylateCrystal structure of the zinc carbapenemase CPHA in complex with the inhibitor pyridine-2,4-dicarboxylate
Structural highlights
FunctionBLAB_AERHY Can hydrolyze carbapenem compounds. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedVarious 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 nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-beta-lactamases. 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 Jun;51(6):2136-42. Epub 2007 Feb 16. PMID:17307979[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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