1bi8
From Proteopedia
(New page: 200px<br /> <applet load="1bi8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bi8, resolution 2.8Å" /> '''MECHANISM OF G1 CYCL...) |
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| - | [[Image:1bi8.gif|left|200px]]<br /> | + | [[Image:1bi8.gif|left|200px]]<br /><applet load="1bi8" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1bi8" size=" | + | |
caption="1bi8, resolution 2.8Å" /> | caption="1bi8, resolution 2.8Å" /> | ||
'''MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURES CDK6-P19INK4D INHIBITOR COMPLEX'''<br /> | '''MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURES CDK6-P19INK4D INHIBITOR COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of | + | 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== | ==About this Structure== | ||
| - | 1BI8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1BI8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BI8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Jeffrey, P | + | [[Category: Jeffrey, P D.]] |
| - | [[Category: Lee, J | + | [[Category: Lee, J O.]] |
| - | [[Category: Pavletich, N | + | [[Category: Pavletich, N P.]] |
| - | [[Category: Russo, A | + | [[Category: Russo, A A.]] |
[[Category: Tong, L.]] | [[Category: Tong, L.]] | ||
[[Category: cdk]] | [[Category: cdk]] | ||
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[[Category: ink4]] | [[Category: ink4]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:55:34 2008'' |
Revision as of 09:55, 21 February 2008
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MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURES CDK6-P19INK4D INHIBITOR 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
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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