2gkl
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Various inhibitors of metallo-beta-lactamases have been reported | + | 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 nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-beta-lactamases. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Competitive | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17307979 17307979] |
[[Category: Aeromonas hydrophila]] | [[Category: Aeromonas hydrophila]] | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
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[[Category: zn]] | [[Category: zn]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:32:36 2008'' |
Revision as of 15:32, 21 February 2008
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Crystal structure of the zinc carbapenemase CPHA in complex with the inhibitor pyridine-2,4-dicarboxylate
Overview
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 nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-beta-lactamases.
About this Structure
2GKL is a Single protein structure of sequence from Aeromonas hydrophila with , and as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:32:36 2008
Categories: Aeromonas hydrophila | Beta-lactamase | Single protein | Dideberg, O. | Garau, G. | GOL | PD2 | ZN | Hydrolase | Inhibitor | Lactamase | Zn
