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The metallo-beta-lactamase GOB is a mono-Zn(II) enzyme with a novel active site. | LitMetric

The metallo-beta-lactamase GOB is a mono-Zn(II) enzyme with a novel active site.

J Biol Chem

Departamento de Química Biológica and Departamento de Microbiología, Instituto de Biología Molecular y Celular de Rosario (IBR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina. Electronic address:

Published: June 2007

AI Article Synopsis

Article Abstract

Metallo-beta-lactamases (MbetaLs) are zinc-dependent enzymes able to hydrolyze and inactivate most beta-lactam antibiotics. The large diversity of active site structures and metal content among MbetaLs from different sources has limited the design of a pan-MbetaL inhibitor. Here we report the biochemical and biophysical characterization of a novel MbetaL, GOB-18, from a clinical isolate of a Gram-negative opportunistic pathogen, Elizabethkingia meningoseptica. Different spectroscopic techniques, three-dimensional modeling, and mutagenesis experiments, reveal that the Zn(II) ion is bound to Asp120, His121, His263, and a solvent molecule, i.e. in the canonical Zn2 site of dinuclear MbetaLs. Contrasting all other related MbetaLs, GOB-18 is fully active against a broad range of beta-lactam substrates using a single Zn(II) ion in this site. These data further enlarge the structural diversity of MbetaLs.

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Source
http://dx.doi.org/10.1074/jbc.M700467200DOI Listing

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