Modulation of Allostery with Multiple Mechanisms by Hotspot Mutations in TetR.

ABSTRACT: Modulating allosteric coupling offers unique opportunities for biomedical applications. Such efforts can benefit from efficient prediction and evaluation of allostery hotspot residues that dictate the degree of cooperativity between distant sites. We demonstrate that effects of allostery hotspot mutations can be evaluated qualitatively and semiquantitatively by molecular dynamics simulations in a bacterial tetracycline repressor (TetR). The simulations recapitulate the effects of these mutations on abolishing the induction function of TetR and provide a rationale for the different rescuabilities observed to restore allosteric coupling of the hotspot mutations. We demonstrate that the same noninducible phenotype could be the result of perturbations in distinct structural and energetic prope

SUBMITTER: Deng J 

PROVIDER: S-EPMC10843641 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature