Inhibitors of CDKs, the CKIs

Negative control of CDK activity in the cell cycle is performed by specific inhibitor proteins known as cyclin-dependent kinase inhibitors, CKIs (review Morgan, 1995 Pines, 1995 Peter, 1997). These are a heterogenous family of proteins that may associate with a CDK or with a CDK-cyclin complex in a reversible maimer, inhibiting CDK activity. 

The CDKs may be divided into two groups based on sequence homology  

The members of the CIP/KIP family inhibit all G1 phase CDK-cyclin complexes (Fig. 13.10). The inhibitors of the INK family prefentially bind to CDK4 and CDK6 complexes. 

A) Ribbon diagram of the complex showing the ThrlbO phosphate (Thr-P 160) and bound ATP. CycUn A is in light grey, CDK2 in dark grey. 

B) Diagram of the multivalent interactions of Thr-P 160 at the CDK2-Cychn A interface. Thr-P 160 forms contacts to ArgSO of the PSTAIRE hehx, to ArglSO of the T-loop, to Argl26 which is close to the catalytic Aspl27 and to De270 of Cyclin A (From Johnson and Reilly (1996), with permission). 

---