Decoding the Interactions Regulating the Active State Mechanics of Eukaryotic Protein Kinases.

ABSTRACT: Eukaryotic protein kinases regulate most cellular functions by phosphorylating targeted protein substrates through a highly conserved catalytic core. In the active state, the catalytic core oscillates between open, intermediate, and closed conformations. Currently, the intramolecular interactions that regulate the active state mechanics are not well understood. Here, using cAMP-dependent protein kinase as a representative model coupled with biochemical, biophysical, and computational techniques, we define a set of highly conserved electrostatic and hydrophobic interactions working harmoniously to regulate these mechanics. These include the previously identified salt bridge between a lysine from the β3-strand and a glutamate from the αC-helix as well as an electrostatic interaction between

SUBMITTER: Meharena HS 

PROVIDER: S-EPMC5130182 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature