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

Author(s): Maria F. Mojica, Robert A. Bonomo, Walter Fast.

Journal Name: Current Drug Targets

Volume 17 , Issue 9 , 2016

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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.

Keywords: β-lactams, Metallo-β-Lactamases, β-lactamase inhibitors, antibiotic resistance.

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Article Details

VOLUME: 17
ISSUE: 9
Year: 2016
Page: [1029 - 1050]
Pages: 22
DOI: 10.2174/1389450116666151001105622
Price: $58

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