Structural Insights and role of Metallo-B-Lactamase Inhibitors

Abstract

The breakdown of the β-lactam ring is catalyzed by metallo-β-lactamases (MBLs), which in turn impart resistance to carbapenems and other β-lactam antibiotics. Due to a lack of adequate treatment options, the fast spread of MBL-producing bacteria poses a serious threat to public health. The creation of effective MBL has therefore been the focus of much study inhibitors capable of restoring β-lactam efficacy. This study provides a comprehensive review of the structural features of MBLs, with a focus regarding the design of the active site and the coordination of metal ions, which are critical for the enzyme’s catalytic activity. A common catalytic mechanism with comparable reaction species is shared by MBLs, notwithstanding their structural diversity. In this article, we detail a variety of MBL inhibitors that imitate substrate, transition state, intermediate, and product species that are produced during hydrolysis. Within the context of MBLs' mechanism, new inhibitors based on boron and thiol have recently been developed, and we take a look at their development. We may also bring up Zn(II) ions are necessary for substrate binding and catalysis, making chelators a potential tactic.