Metallo-β-lactamases:: does it take two to tango?

Metallo-beta-lactamases are a subset of zinc hydrolases able to hydrolyze the beta-lactam ring of several antibiotics. The number of structural and mechanistic studies on these metalloenzymes has grown steadily in the recent years, due to their biomedical relevance in bacterial resistance. Crystallographic and spectroscopic studies on enzymes from different sources indicate that: a conserved metal ligand set is able to bind either one of two metal equivalents. Even if both the mono- and bimetallic forms of these enzymes seem to be active in most cases, the binuclear species appear to be the most fit for conferring antibiotic resistance. The active nucleophile is a water/hydroxide molecule which has been found binding to either one or two Zn(II)s. The affinity for binding the second metal ion equivalent is related to the needs of the different enzymes in their natural environments. The exact role of the second Zn(II) is still unknown, but it has been proposed that it may help in positioning the substrate for the nucleophilic attack. (C) 1999 Elsevier Science S.A. All rights reserved.