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
04/04/2007Pubmed ID
17403673DOI
10.1074/jbc.M700467200Scopus ID
2-s2.0-34547104390 (requires institutional sign-in at Scopus site) 72 CitationsAbstract
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 AJAuthor
Brian Bennett D.Phil. Professor and Chair in the Physics department at Marquette UniversityMESH terms used to index this publication - Major topics in bold
Binding SitesCloning, Molecular
DNA
Flavobacterium
Genetic Vectors
Hydrolysis
Inhibitory Concentration 50
Kinetics
Models, Chemical
Molecular Sequence Data
Mutagenesis
Mutagenesis, Site-Directed
Spectrophotometry
Zinc
beta-Lactamases