Subdomain II of Kinase Domain of Protein Kinase A

The structure of Subdomain II consists of a beta sheet (3)with a small alpha helix toward the end. In the picture above subdomain II is the red ribbon structure. From sequence alignment with similar protein kinases, the alpha helix is not particularly well conserved. This subdomain contains an important,invariant lysine residue that is present in all of the protein kinases, in the beta sheet portion of the subdomain.The invariant lysine residue is represented by the spacefilling model in the middle of the subdomain. In PKA the lysine is at postion 72, and it has been shown to be extremely important to the optimum activity of the enzyme. This was found by covalent modification with an MgATP analog. (Knighton et al.) Lys72 forms a salt bridge with Glu91, which is an invariant residue in subdomain III. This is thought to stabilize interactions between Lys72 and the alpha and beta phosphates of ATP. Lys72 also lies in close proximity to Asp184.