Computational and experimental analyses of alanine racemase suggest new avenues for developing allosteric small-molecule antibiotics.

ABSTRACT: Given the ever-present threat of antibacterial resistance, there is an urgent need to identify new antibacterial drugs and targets. One such target is alanine racemase (Alr), an enzyme required for bacterial cell-wall biosynthesis. Alr is an attractive drug target because it is essential for bacterial survival but is absent in humans. Existing drugs targeting Alr lack specificity and have severe side effects. We here investigate alternative mechanisms of Alr inhibition. Alr functions exclusively as an obligate homodimer, so we probed seven conserved interactions on the dimer interface, distant from the enzymatic active site, to identify possible allosteric influences on activity. Using the Alr from Mycobacterium tuberculosis (MT) as a model, we found that the Lys261/Asp135 salt bridge is c

SUBMITTER: van Wieren A 

PROVIDER: S-EPMC10524904 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature