1bi7
From Proteopedia
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'''MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX''' | '''MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX''' | ||
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[[Category: Russo, A A.]] | [[Category: Russo, A A.]] | ||
[[Category: Tong, L.]] | [[Category: Tong, L.]] | ||
| - | [[Category: | + | [[Category: Cdk]] |
| - | [[Category: | + | [[Category: Cell cycle]] |
| - | [[Category: | + | [[Category: Cyclin dependent kinase]] |
| - | + | [[Category: Cyclin dependent kinase inhibitory protein]] | |
| - | [[Category: | + | [[Category: Ink4]] |
| - | [[Category: | + | [[Category: Mts1]] |
| - | [[Category: | + | [[Category: Multiple tumor suppressor]] |
| - | [[Category: | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:32:38 2008'' |
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 08:32, 2 May 2008
MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX
Overview
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.
About this Structure
1BI7 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a., Russo AA, Tong L, Lee JO, Jeffrey PD, Pavletich NP, Nature. 1998 Sep 17;395(6699):237-43. PMID:9751050 Page seeded by OCA on Fri May 2 11:32:38 2008
