Subdomain VII of Cyclin-Dependent Kinase 2
Subdomain VII in Cdk2, residues 139-157, is different from that of
PKA. PKA has a beta-strand-loop-beta-strand structure, whereas Cdk2 has an
alpha-helix, alpha-L12, in place of the second beta-strand(beta-9). The helix
runs from residues 147-151. The ATP binding site is adjacent to the short
alpha-L12 helix. Because of the alpha-L12helix, the alpha-1 helix is further
from the ATP molecule. Therefore the salt bridge between Glu51 and Lys33 is
not present in the Cdk2 apoenzyme as it is in cAPK between Glu91 and Lys72.
binding, however, melts the alpha-L12 helix and replaces it with
the necessary beta-strand 9. This event allows the salt bridge to form,
thus activating Cdk2.
The conformation of the alpha-L12 helix also prevents the residues
in the DGF motif at the N-terminal of the helix (Asp145, Phe146, Gly148)
from interacting, as they do in cAPK. In cAPK, they hydrogen bond to form
a loop between the backbone carbonyl of Asp184 and the backbone amide of Gly186.
In Cdk2, the Asp145 side chain has a different orientation due to the
presence of the alpha-L12 helix and the positioning of the side chain of
Lys33 side chain.
Subdomain VII in Cdk2 also contains the beginning of the T-loop.
The T-loop runs from residues 152-170, and contains the Thr160
phosphorylation site, discussed in the