The regulatory subunit of cAMP dependent protein kinase has two sites at which cAMP can bind. The conformational change induced by this binding releases the catalytic subunit, so it can perform its function.

Each domain, A and B have one cAMP binding site. the site in Domain A is referred to as binding site A and the other is binding site B. In both sites, the nucleotide is bound in a syn conformation, with electrostatic and hydrogen bonding interactions between the protein and the phosphates and ribose ring. The interactions with the ribose and phosphates occur through the highly _conserved residues_ present in the segment linking beta strands 6 and 7 (picture) The adenine is bound primarily by stacking and hydrophobic interactions with residues present in and close to the C helix.

Site A

Site A has 3 conserved residues that interact with the cAMP and form the core or the binding site: Glu200 and Arg 209 are present in the short helix between beta sheets 6 and 7, and interact with the phosphate and ribose. Trp 260 stacks its aromatic sidechain with the adenine ring.

cAMP is in yellow, residues are in green and labelesd

Site B

Site B has 3 similar residues that bind the cAMP. Glu324 and Arg333 interact with the ribose and the phosphate, while the aromatic sidechain of Tyr371 interacts with the adenine ring.
cAMP is in yellow, residues are in green and labelesd


In both cases, the Glu residues interact with the 2' OH of the ribose, and the Arg residues interact with the phosphate. The aromatic (Trp 260 for A and Tyr 371 for B) stacks with the adenine ring. These active site residues also interact with a network of other residues throughout the protein. Through this network a conformational change is made when cAMP binds to the binding site.