Structural Insights into the Inhibition of the Extended-Spectrum β-Lactamase PER-2 by Avibactam.

ABSTRACT: The diazabicyclooctane (DBO) avibactam (AVI) reversibly inactivates most serine-β-lactamases. Previous investigations showed that inhibition constants of AVI toward class A PER-2 are reminiscent of values observed for class C and D β-lactamases (i.e., k2/K of ≈103 M-1 s-1) but lower than other class A β-lactamases (i.e., k2/K = 104 to 105 M-1 s-1). Herein, biochemical and structural studies were conducted with PER-2 and AVI to explore these differences. Furthermore, biochemical studies on Arg220 and Thr237 variants with AVI were conducted to gain deeper insight into the mechanism of PER-2 inactivation. The main biochemical and structural observations revealed the following: (i) both amino-acid substitutions in Arg220 and the rich hydrophobic content in the active site hinder the binding of

SUBMITTER: Ruggiero M 

PROVIDER: S-EPMC6709463 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature