Uncoupling Catalytic and Binding Functions in the Cyclic AMP-Dependent Protein Kinase A.

ABSTRACT: The canonical function of kinases is to transfer a phosphoryl group to substrates, initiating a signaling cascade; while their non-canonical role is to bind other kinases or substrates, acting as scaffolds, competitors, and signal integrators. Here, we show how to uncouple kinases' dual function by tuning the binding cooperativity between nucleotide (or inhibitors) and substrate allosterically. We demonstrate this new concept for the C subunit of protein kinase A (PKA-C). Using thermocalorimetry and nuclear magnetic resonance, we found a linear correlation between the degree of cooperativity and the population of the closed state of PKA-C. The non-hydrolyzable ATP analog (ATPγC) does not follow this correlation, suggesting that changing the chemical groups around the phosphoester bond can

SUBMITTER: Kim J 

PROVIDER: S-EPMC4775281 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature