Structural Basis for Enhancement of Carbapenemase Activity in the OXA-51 Family of Class D β-Lactamases.

ABSTRACT: Class D β-lactamases of Acinetobacter baumannii are enzymes of the utmost clinical importance, producing resistance to last resort carbapenem antibiotics. Although the OXA-51-like enzymes constitute the largest family of class D β-lactamases, they are poorly studied and their importance in conferring carbapenem resistance is controversial. We present the detailed microbiological, kinetic, and structural characterization of the eponymous OXA-51 β-lactamase. Kinetic studies show that OXA-51 has low catalytic efficiency for carbapenems, primarily due to the low affinity of the enzyme for these substrates. Structural studies demonstrate that this low affinity results from the obstruction of the enzyme active site by the side chain of Trp222, which presents a transient steric barrier to an inco

SUBMITTER: Smith CA 

PROVIDER: S-EPMC4546549 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature