Structure
The conformation of the Cdk2 active site changes dramatically upon cyclin binding and CAK phosphorylation. The active site of Cdk2 lies in a cleft between the two lobes of the kinase. ATP binds deep within the cleft and its phosphate is oriented outwards. Protein substrates bind to the entrance of the active site cleft.
In its inactive form, Cdk2 cannot bind substrate because the entrance of its active site is blocked by the T-loop. Inactive Cdk2 also has a misoriented ATP binding site. When Cdk2 is inactive, the small L12 helix pushes the large PSTAIRE helix outwards. The PSTAIRE helix contains a residue, glutamate 51, that is important for positioning the ATP phosphates.
When cyclinA binds, several conformational changes take place. The T-loop moves out of active site entrance and no longer blocks the substrate binding site. The PSTAIRE helix moves in. The L12 helix becomes a beta strand. This allows glutamate 51 to interact with lysine 33. Aspartate 145 also changes position. Together these structural changes allow ATP phosphates to bind correctly.
When CAK phosphorylates Cdk's threonine residue160, the T-loop flattens and interacts more closely with cyclin A. Phosphorylation also allows the Cdk to interact more effectively with substrates that contain the SPXK sequence. Phosphorylation also increases the activity of cyclinA-Cdk2 complex. Different cyclins produce different conformation changes in Cdk.
Image Link - Structural Basis of Cdk Activation
http://www.oup.com/uk/orc/bin/9780199206100/resources/figures/nsp-cellcycle-3-4-3_12.jpg
Credit to: Oxford University Press "Morgan: The Cell Cycle"
Read more about this topic: CDK-activating Kinase
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