| Literature DB >> 17403673 |
Jorgelina Morán-Barrio1, Javier M González, María Natalia Lisa, Alison L Costello, Matteo Dal Peraro, Paolo Carloni, Brian Bennett, David L Tierney, Adriana S Limansky, Alejandro M Viale, Alejandro J Vila.
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.Entities:
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Year: 2007 PMID： 17403673 DOI： 10.1074/jbc.M700467200
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157