Electrostatic Interactions as Mediators in the Allosteric Activation of Protein Kinase A RIα.

ABSTRACT: Close-range electrostatic interactions that form salt bridges are key components of protein stability. Here we investigate the role of these charged interactions in modulating the allosteric activation of protein kinase A (PKA) via computational and experimental mutational studies of a conserved basic patch located in the regulatory subunit's B/C helix. Molecular dynamics simulations evidenced the presence of an extended network of fluctuating salt bridges spanning the helix and connecting the two cAMP binding domains in its extremities. Distinct changes in the flexibility and conformational free energy landscape induced by the separate mutations of Arg239 and Arg241 suggested alteration of cAMP-induced allosteric activation and were verified through in vitro fluorescence polarization assa

SUBMITTER: P Barros E 

PROVIDER: S-EPMC5495472 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature