期刊
CURRENT DRUG TARGETS
卷 17, 期 9, 页码 1029-1050出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389450116666151001105622
关键词
beta-lactams; Metallo-beta-Lactamases; beta-lactamase inhibitors; antibiotic resistance
资金
- Robert. A. Welch Foundation [F1572]
- National Institutes of General Medical Sciences of the National Institutes of Health [GM111926]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01AI063517, R01AI100560]
- Cleveland Department of Veterans Affairs
- Veterans Affairs Merit Review Program [1I01BX001974]
- Geriatric Research Education and Clinical Center [VISN 10]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI063517, R01AI100560, R01AI072219] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM111926] Funding Source: NIH RePORTER
- Veterans Affairs [I01BX001974] Funding Source: NIH RePORTER
Metallo-beta-Lactamases (MBLs) are class B beta-lactamases that hydrolyze almost all clinically-available beta-lactam antibiotics. MBLs feature the distinctive alpha beta/alpha beta 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.
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