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The metallo-beta-lactamase GOB is a mono-Zn(II) enzyme with a novel active site. J Biol Chem 2007 Jun 22;282(25):18286-18293

Date

04/04/2007

Pubmed ID

17403673

DOI

10.1074/jbc.M700467200

Scopus ID

2-s2.0-34547104390 (requires institutional sign-in at Scopus site)   72 Citations

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.

Author List

Morán-Barrio J, González JM, Lisa MN, Costello AL, Peraro MD, Carloni P, Bennett B, Tierney DL, Limansky AS, Viale AM, Vila AJ

Author

Brian Bennett D.Phil. Professor and Chair in the Physics department at Marquette University




MESH terms used to index this publication - Major topics in bold

Binding Sites
Cloning, Molecular
DNA
Flavobacterium
Genetic Vectors
Hydrolysis
Inhibitory Concentration 50
Kinetics
Models, Chemical
Molecular Sequence Data
Mutagenesis
Mutagenesis, Site-Directed
Spectrophotometry
Zinc
beta-Lactamases