Mechanistic Investigations of Metallo-β-lactamase Inhibitors: Strong Zinc Binding Is Not Required for Potent Enzyme Inhibition*.

ABSTRACT: Metallo-β-lactamases (MBLs) are zinc-dependent bacterial enzymes that inactivate essentially all classes of β-lactam antibiotics including last-resort carbapenems. At present there are no clinically approved MBL inhibitors, and in order to develop such agents it is essential to understand their inhibitory mechanisms. Herein, we describe a comprehensive mechanistic study of a panel of structurally distinct MBL inhibitors reported in both the scientific and patent literature. Specifically, we determined the half-maximal inhibitory concentration (IC₅₀ ) for each inhibitor against MBLs belonging to the NDM and IMP families. In addition, the binding affinities of the inhibitors for Zn²⁺ , Ca²⁺  and Mg²⁺  were assessed by using isothermal titration cal

SUBMITTER: Wade N 

PROVIDER: S-EPMC8248298 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature