Metal Substitution in GOB-18 Metallo-β-lactamase

MARÍA NATALIA LISA AND ALEJANDRO J. VILA

Acapulco- México

Congreso; Second Latin American Protein Society Meeting; 2007

Metallo-β-lactamases (MβLs) are zinc dependent enzymes able to hydrolyzeand inactivate most β-lactam antibiotics. The large diversity of active sitestructures and metal content among MβLs from different sources has limited thedesign of a pan-MβL inhibitor. These enzymes have become of great concern inthe medical area as they are becoming widely distributed among pathogens.GOB is a MβL produced by the opportunistic pathogen Elizabethkingiameningoseptica, causative agent of meningitis. We have recently reported thebiochemical and biophysical characterization of GOB-18 (1). The studiesperformed showed that this enzyme is a mono-Zn(II) broad spectrumlactamase. Being that Zn(II) is a silent ion for most spectroscopic techniques,we have used different metal ions as probes for the study of the active site ofGOB-18. Here we present the characterization of different metal derivatives ofthis novel MβL. These new data reveals only one metal binding site whichdisplays a distorted tetrahedral geometry, and that two metal ligands are Hisresidues.