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

MORAN-BARRIO, J.; GONZALEZ, J.; LISA, M.; COSTELLO, A.; PERARO M; CARLONI P; BENNET, B.; TIERNEY, D.; LIMANSKY A; VIALE, A.; VILA, A.

Journal of Biological Chemistry

American Society for Biochemistry and Molecular Biology.

Año: 2007 vol. 282 p. 18286 - 18293

0021-9258

Metallo-beta-lactamases (MBLs) are zinc-dependent enzymes able to hydrolyze and inactivate most beta-lactam antibiotics. The large diversity of active site structures and metal content among MBLs from different sources has limited the design of a pan-MBL inhibitor. Here we report the biochemical and biophysical characterization of a novel MBL, GOB-18, from a clinical isolate of a Gram-negative opportunistic pathogen, Elizabethkingia meningoseptica. Different spectroscopic techniques, 3D 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 MBLs. Contrasting all other related MBLs, 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 MBLs.