Crystal Structure of the P27Kip1 Cyclin-dependent-kinase Inhibitor Bound to the Cyclin A-Cdk2 Complex

The crystal structure of the human p27Kip1 kinase inhibitory domain bound to the phosphorylated cyclin A-cyclin-dependent kinase 2 (Cdk2) complex has been determined at 2.3 angstrom. p27Kip1 binds the complex as an extended structure interacting with both cyclin A and Cdk2. On cyclin A, it binds in a groove formed by conserved cyclin box residues. On Cdk2, it binds and rearranges the amino-terminal lobe and also inserts into the catalytic cleft, mimicking ATP.