Calculating pKa values in the cAMP-dependent protein kinase: the effect of conformational change and ligand binding.

ABSTRACT: The conformational change observed upon ligand binding and phosphorylation for the cAMP-dependent protein kinase (protein kinase A-PKA) is of high importance for the regulation of its activity. We calculate pKa values and net charges for 18 3D structures of PKA in various conformations and liganded states to examine the role of electrostatics in ligand binding and activation. We find that the conformational change of PKA takes place without any significant net proton uptake/release at all pH values, thus indicating that PKA has evolved to reduce any pH-dependent barriers to the conformational motion. We furthermore find that the binding of ligands induces large changes in the net charge of PKA at most pH values, but significantly, we find that the net charge difference at physiological pH

SUBMITTER: Bjarnadottir U 

PROVIDER: S-EPMC3009415 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature