The structure of the Cdk2–cyclin A–p27 complex, as determined by X-ray crystallography, reveals that the inhibitor p27 (red) stretches across the top of the cyclin–Cdk complex. Only the amino-terminal region of p27 is shown in the structure. The amino- terminal end of this fragment contains an RXL motif that interacts with the hydrophobic patch of cyclin A. The carboxy-terminal end of the p27 fragment interacts extensively with the beta sheet of Cdk2, causing extensive disruptions to its structure; p27 also inserts into the ATP-binding site of Cdk2 and directly inhibits ATP binding. (PDB 1jsu)
A cyclin-dependent kinase complex (CDKC, cyclin-CDK) is a protein complex formed by the association of an inactive catalytic subunit of a protein kinase, cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin.[1] Once cyclin-dependent kinases bind to cyclin, the formed complex is in an activated state. Substrate specificity of the activated complex is mainly established by the associated cyclin within the complex. Activity of CDKCs is controlled by phosphorylation of target proteins, as well as binding of inhibitory proteins.[2]
^Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci. 2005 Nov;30(11):630-41
^Lodish H, Baltimore D, Berk A, Zipursky SL, Matsudaira P, Darnell J. 1995. Molecular Cell Biology. 3rd Ed. New York: Scientific American Books
