Protein Kinase A: Difference between revisions

PKA consists of a regulatory dimer, which each regulatory subunit attached to a catalytic subunit. When cAMP levels are low, the enzyme is intact, forming  the R2C2 complex. However, when cAMP levels are high, two cAMP molecules bind to the regulatory sites of the complex, which leads to the dissociation of the R2C2 complex into an R2 subunit and two C subunits. When cAMP binds to the R chains, the binding allosterically removes the <scene name='58/582909/Psuedosubstrate/1'>pseudosubstrate</scene> sequences, Arg-Arg-Gly-Ala-Ile, out of the catalytic sites. This psuedosubstrate sequence of R occupies the catalytic site of C and prevents it from interacting with protein substrates. The only difference between the pseudosubstrate sequence and the sequence for phophorylations is the alanine in place of the serine. The pseudosubstrate binds to PKA through specific interactions. The guanidinium group of the first arginine forms an ion pair with the carboxylate groups of the glutamate residue, Glu 127, of the enzyme, forming a salt bridge. In the same way, the second arginine interacts with two other carboxylate groups, forming two more salt bridges. Two leucine residues of the enzyme form a hydrophobic groove in which the nonpolar side chain of isoleucine fits into. The scene is shown here. Once released, the two enzymatically active C subunites are free to phosphorylate proteins.  

PKA is inactivated by a feedback mechanism. PKA activates phosphodiesterase, which converts cAMP back to ATP. This reduces the amount of cAMP that can activate PKA.  

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