B1-Metallo-β-Lactamases: Where Do We Stand?

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:

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.

Cite this article as:

F. Mojica Maria, A. Bonomo Robert and Fast Walter, B1-Metallo-β-Lactamases: Where Do We Stand?, Current Drug Targets 2016; 17 (9) . https://dx.doi.org/10.2174/1389450116666151001105622