1bi8

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[[Image:1bi8.gif|left|200px]]
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{{STRUCTURE_1bi8| PDB=1bi8 | SCENE= }}
{{STRUCTURE_1bi8| PDB=1bi8 | SCENE= }}
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'''MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURES CDK6-P19INK4D INHIBITOR COMPLEX'''
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===MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURES CDK6-P19INK4D INHIBITOR COMPLEX===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 9751050 is the PubMed ID number.
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{{ABSTRACT_PUBMED_9751050}}
==About this Structure==
==About this Structure==
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[[Category: Cyclin dependent kinase inhibitory protein]]
[[Category: Cyclin dependent kinase inhibitory protein]]
[[Category: Ink4]]
[[Category: Ink4]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:32:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:12:22 2008''

Revision as of 16:12, 30 June 2008

Image:1bi8.png

Template:STRUCTURE 1bi8

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

Template:ABSTRACT PUBMED 9751050

About this Structure

1BI8 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

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