Protein kinase G family
protein kinase g family
The protein kinase G family comprises two closely related genes (PRKG1 and PRKG2) that encode cGMP-dependent serine/threonine kinases (often referred to as cGKs). These enzymes have a rod-like structure and are activated at submicromolar to micromolar concentrations of cGMP. They are composed of three functional domains: an N-terminal (A) domain, a regulatory (R) domain, and a catalytic (C) domain. The regulatory domain contains two tandem cGMP-binding sites that interact allosterically and bind cGMP with high and low affinity. Occupation of both binding sites induces a large change in secondary structure to yield a more elongated molecule. The catalytic domain contains the MgATP- and peptide-binding pockets. Binding of cGMP to both sites in the R domain releases the inhibition of the catalytic center by the N-terminal autoinhibitory/pseudosubstrate site and allows the phosphorylation of serine/threonine residues in target proteins and in the N-terminal autophosphorylation site. In addition to controlling activation and inhibition of the catalytic center, the N terminus has two other functions: dimerization, cGKs are homodimers that are held together by a leucine zipper present in the N terminus, and targeting, the enzymes are targeted to different subcellular localizations by their N termini.