Genetic and structural characterization of an L201P global suppressor substitution in TEM-1 beta-lactamase.

ABSTRACT: TEM-1 beta-lactamase confers bacterial resistance to penicillin antibiotics and has acquired mutations that permit the enzyme to hydrolyze extended-spectrum cephalosporins or to avoid inactivation by beta-lactamase inhibitors. However, many of these substitutions have been shown to reduce activity against penicillin antibiotics and/or result in loss of stability for the enzyme. In order to gain more information concerning the tradeoffs associated with active site substitutions, a genetic selection was used to find second site mutations that partially restore ampicillin resistance levels conferred by an R244A active site TEM-1 beta-lactamase mutant. An L201P substitution distant from the active site that enhanced ampicillin resistance levels and increased protein expression levels of the R2

SUBMITTER: Marciano DC 

PROVIDER: S-EPMC2644635 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature