1zkj

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{{STRUCTURE_1zkj| PDB=1zkj | SCENE= }}
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'''Structural Basis for the Extended Substrate Spectrum of CMY-10, a Plasmid-Encoded Class C beta-lactamase'''
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===Structural Basis for the Extended Substrate Spectrum of CMY-10, a Plasmid-Encoded Class C beta-lactamase===
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==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Extended spectrum beta-lactamase]]
[[Category: Extended spectrum beta-lactamase]]
[[Category: Plasmid]]
[[Category: Plasmid]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:13:47 2008''

Revision as of 16:13, 28 July 2008

Image:1zkj.png

Template:STRUCTURE 1zkj

Structural Basis for the Extended Substrate Spectrum of CMY-10, a Plasmid-Encoded Class C beta-lactamase

Template:ABSTRACT PUBMED 16677302

About this Structure

1ZKJ is a Single protein structure of sequence from Enterobacter aerogenes. 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

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