1ZKJ

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

Summary for 1ZKJ

• Entry DOI: 10.2210/pdb1zkj/pdb
• Descriptor: extended-spectrum beta-lactamase, ZINC ION, ACETIC ACID, ... (4 entities in total)
• Functional Keywords: extended spectrum beta-lactamase, cmy-10, plasmid, class c, hydrolase
• Biological source: Enterobacter aerogenes
• Total number of polymer chains: 1
• Total formula weight: 39106.91

Authors

Cha, S.S.,Jung, H.I.,An, Y.J.,Lee, S.H. (deposition date: 2005-05-03, release date: 2006-04-18, Last modification date: 2024-03-13)

Primary citation

Kim, J.Y.,Jung, H.I.,An, Y.J.,Lee, J.H.,Kim, S.J.,Jeong, S.H.,Lee, K.J.,Suh, P.G.,Lee, H.S.,Lee, S.H.,Cha, S.S.
Structural basis for the extended substrate spectrum of CMY-10, a plasmid-encoded class C beta-lactamase.
Mol.Microbiol., 60:907-916, 2006

PubMed Abstract: 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.

PubMed: 16677302
DOI: 10.1111/j.1365-2958.2006.05146.x

Experimental method

X-RAY DIFFRACTION (1.55 Å)