1BI8

MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURES CDK6-P19INK4D INHIBITOR COMPLEX

Summary for 1BI8

• Entry DOI: 10.2210/pdb1bi8/pdb
• Descriptor: CYCLIN-DEPENDENT KINASE 6, CYCLIN-DEPENDENT KINASE INHIBITOR (2 entities in total)
• Functional Keywords: cyclin dependent kinase, cyclin dependent kinase inhibitory protein, cdk, ink4, cell cycle, complex (kinase-inhibitor), complex (kinase-inhibitor) complex, complex (kinase/inhibitor)
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 109420.99

Authors

Russo, A.A.,Tong, L.,Lee, J.O.,Jeffrey, P.D.,Pavletich, N.P. (deposition date: 1998-06-22, release date: 1999-01-13, Last modification date: 2024-04-03)

Primary citation

Russo, A.A.,Tong, L.,Lee, J.O.,Jeffrey, P.D.,Pavletich, N.P.
Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a.
Nature, 395:237-243, 1998

PubMed Abstract: The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of the cell cycle and their inhibitor, the p16INK4a tumour suppressor, have a central role in cell proliferation and in tumorigenesis. The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next to the ATP-binding site of the catalytic cleft, opposite where the activating cyclin subunit binds. They prevent cyclin binding indirectly by causing structural changes that propagate to the cyclin-binding site. The INK4 inhibitors also distort the kinase catalytic cleft and interfere with ATP binding, which explains how they can inhibit the preassembled Cdk4/6-cyclin D complexes as well. Tumour-derived mutations in INK4a and Cdk4 map to interface contacts, solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16INK4a.

PubMed: 9751050
DOI: 10.1038/26155

Experimental method

X-RAY DIFFRACTION (2.8 Å)