Title:B1-Metallo-β-Lactamases: Where Do We Stand?
VOLUME: 17 ISSUE: 9
Author(s):Maria F. Mojica, Robert A. Bonomo and Walter Fast
Affiliation:Medical Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Blvd., Cleveland, OH 44106, USA., Division of Medicinal Chemistry, College of Pharmacy, University of Texas, Austin TX, 78712, USA.
Keywords:β-lactams, Metallo-β-Lactamases, β-lactamase inhibitors, antibiotic resistance.
Abstract:Metallo-β-Lactamases (MBLs) are class B β-lactamases that hydrolyze almost
all clinically-available β-lactam antibiotics. MBLs feature the distinctive αβ/βα
sandwich fold of the metallo-hydrolase/oxidoreductase superfamily and possess a shallow
active-site groove containing one or two divalent zinc ions, flanked by flexible
loops. According to sequence identity and zinc ion dependence, MBLs are classified into three subclasses (B1, B2 and
B3), of which the B1 subclass enzymes have emerged as the most clinically significant. Differences among the active site
architectures, the nature of zinc ligands, and the catalytic mechanisms have limited the development of a common inhibitor.
In this review, we will describe the molecular epidemiology and structural studies of the most prominent representatives
of class B1 MBLs (NDM-1, IMP-1 and VIM-2) and describe the implications for inhibitor design to counter this
growing clinical threat.
