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 co-operativity between distant sites. We demonstrate that effects of allostery hotspot mutations can be evaluated qualitatively and semi-quantitatively 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 degrees of rescuability observed to restore allosteric coupling of the hotspot mutations. We demonstrate that the same non-inducible phenotype could be the result of perturbations in distinct structural and ene

SUBMITTER: Deng J 

PROVIDER: S-EPMC10614727 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature