Role of the Conserved Disulfide Bridge in Class A Carbapenemases.

ABSTRACT: Some members of the class A β-lactamase family are capable of conferring resistance to the last resort antibiotics, carbapenems. A unique structural feature of these clinically important enzymes, collectively referred to as class A carbapenemases, is a disulfide bridge between invariant Cys⁶⁹ and Cys²³⁸ residues. It was proposed that this conserved disulfide bridge is responsible for their carbapenemase activity, but this has not yet been validated. Here we show that disruption of the disulfide bridge in the GES-5 carbapenemase by the C69G substitution results in only minor decreases in the conferred levels of resistance to the carbapenem imipenem and other β-lactams. Kinetic and circular dichroism experiments with C69G-GES-5 demonstrate that this small drop in antibi

SUBMITTER: Smith CA 

PROVIDER: S-EPMC5063999 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature