Document Type

Article

Language

eng

Format of Original

8 p.

Publication Date

6-22-2007

Publisher

American Society for Biochemistry and Molecular Biology

Source Publication

Journal of Biological Chemistry

Source ISSN

0021-9258

Original Item ID

doi: 10.1074/jbc.M700467200

Abstract

Metallo-β-lactamases (MβLs) are zinc-dependent enzymes able to hydrolyze and inactivate most β-lactam antibiotics. The large diversity of active site structures and metal content among MβLs from different sources has limited the design of a pan-MβL inhibitor. Here we report the biochemical and biophysical characterization of a novel MβL, 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 MβLs. Contrasting all other related MβLs, GOB-18 is fully active against a broad range of β-lactam substrates using a single Zn(II) ion in this site. These data further enlarge the structural diversity of MβLs.

Comments

Published version. Journal of Biological Chemistry, Vol. 282, No. 25 (June 22, 2007): 18286-18293. DOI. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc. Used with permission.

Brian Bennett was affiliated with the Medical College of Wisconsin at the time of publication.

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