Subdomain II of Cyclin-Dependent Kinase 2


Subdomain II includes residues 26-43, which comprises the beta-3 strand of the small lobe. Beta-3 is found between loop regions 3 and 4. Cdk2 does not have the alpha-helix seen in subdomain II in some of the other protein kinase structures, such as PKA. The conserved lysine needed for maximum enzyme function is at position 33 in beta-3 of the small lobe. In cAPK, this lysine functions in anchorage and orientation of the ATP and it forms a salt bridge with the carboxyl group of the conserved Glu91 in subdomain III. In Cdk2, this does not occur because the presense of the alpha-L12 helix, which is not present in cAPK, increases the distance between Lys33 and Glu51. cAPK instead has a beta-strand.

In mutation experiments, it was found that the residues Arg36, Asp38, Glu40, and Glu42 of subdomain II must be intact in order for cyclin to bind.