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1zkj
From Proteopedia
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Structural Basis for the Extended Substrate Spectrum of CMY-10, a Plasmid-Encoded Class C beta-lactamase
Overview
The emergence and dissemination of extended-spectrum (ES) beta-lactamases, induce therapeutic failure and a lack of eradication of clinical isolates, even by third-generation beta-lactam antibiotics like ceftazidime. CMY-10, is a plasmid-encoded class C beta-lactamase with a wide spectrum of, substrates. Unlike the well-studied class C ES beta-lactamase from, Enterobacter cloacae GC1, the Omega-loop does not affect the active site, conformation and the catalytic activity of CMY-10. Instead, a, three-amino-acid deletion in the R2-loop appears to be responsible for the, ES activity of CMY-10. According to the crystal structure solved at 1.55 A, resolution, the deletion significantly widens the R2 active site, which, accommodates the R2 side-chains of beta-lactam antibiotics. This, observation led us to demonstrate the hydrolysing activity of CMY-10, towards imipenem with a long R2 substituent. The forced mutational, analyses of P99 beta-lactamase reveal that the introduction of deletion, mutations into the R2-loop is able to extend the substrate spectrum of, class C non-ES beta-lactamases, which is compatible with the isolation of, natural class C ES enzymes harbouring deletion mutations in the R2-loop., Consequently, the opening of the R2 active site by the deletion of some, residues in the R2-loop can be considered as an operative molecular, strategy of class C beta-lactamases to extend their substrate spectrum.
About this Structure
1ZKJ is a Single protein structure of sequence from Enterobacter aerogenes with and as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
Structural basis for the extended substrate spectrum of CMY-10, a plasmid-encoded class C beta-lactamase., Kim JY, Jung HI, An YJ, Lee JH, Kim SJ, Jeong SH, Lee KJ, Suh PG, Lee HS, Lee SH, Cha SS, Mol Microbiol. 2006 May;60(4):907-16. PMID:16677302
Page seeded by OCA on Tue Jan 29 17:36:54 2008
