1g3n: Difference between revisions
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[[Image:1g3n.jpg|left|200px]] | [[Image:1g3n.jpg|left|200px]] | ||
'''STRUCTURE OF A P18(INK4C)-CDK6-K-CYCLIN TERNARY COMPLEX''' | {{Structure | ||
|PDB= 1g3n |SIZE=350|CAPTION= <scene name='initialview01'>1g3n</scene>, resolution 2.9Å | |||
|SITE= | |||
|LIGAND= | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] | |||
|GENE= CYCLIN-DEPENDENT KINASE 6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), P18(INK4C) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), K-CYCLIN (VIRAL CYCLIND HOMOLOG) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10376 Human herpesvirus 4]) | |||
}} | |||
'''STRUCTURE OF A P18(INK4C)-CDK6-K-CYCLIN TERNARY COMPLEX''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1G3N is a [ | 1G3N is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G3N OCA]. | ||
==Reference== | ==Reference== | ||
Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors., Jeffrey PD, Tong L, Pavletich NP, Genes Dev. 2000 Dec 15;14(24):3115-25. PMID:[http:// | Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors., Jeffrey PD, Tong L, Pavletich NP, Genes Dev. 2000 Dec 15;14(24):3115-25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11124804 11124804] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Human herpesvirus 4]] | [[Category: Human herpesvirus 4]] | ||
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[[Category: viral cyclin]] | [[Category: viral cyclin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:17:44 2008'' | ||
Revision as of 12:17, 20 March 2008
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| , resolution 2.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | CYCLIN-DEPENDENT KINASE 6 (Homo sapiens), P18(INK4C) (Homo sapiens), K-CYCLIN (VIRAL CYCLIND HOMOLOG) (Human herpesvirus 4) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF A P18(INK4C)-CDK6-K-CYCLIN TERNARY COMPLEX
OverviewOverview
The cyclin-dependent kinases 4 and 6 (Cdk4/6) that drive progression through the G(1) phase of the cell cycle play a central role in the control of cell proliferation, and CDK deregulation is a frequent event in cancer. Cdk4/6 are regulated by the D-type cyclins, which bind to CDKs and activate the kinase, and by the INK4 family of inhibitors. INK4 proteins can bind both monomeric CDK, preventing its association with a cyclin, and also the CDK-cyclin complex, forming an inactive ternary complex. In vivo, binary INK4-Cdk4/6 complexes are more abundant than ternary INK4-Cdk4/6-cyclinD complexes, and it has been suggested that INK4 binding may lead to the eventual dissociation of the cyclin. Here we present the 2.9-A crystal structure of the inactive ternary complex between Cdk6, the INK4 inhibitor p18(INK4c), and a D-type viral cyclin. The structure reveals that p18(INK4c) inhibits the CDK-cyclin complex by distorting the ATP binding site and misaligning catalytic residues. p18(INK4c) also distorts the cyclin-binding site, with the cyclin remaining bound at an interface that is substantially reduced in size. These observations support the model that INK4 binding weakens the cyclin's affinity for the CDK. This structure also provides insights into the specificity of the D-type cyclins for Cdk4/6.
About this StructureAbout this Structure
1G3N is a Protein complex structure of sequences from Homo sapiens and Human herpesvirus 4. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors., Jeffrey PD, Tong L, Pavletich NP, Genes Dev. 2000 Dec 15;14(24):3115-25. PMID:11124804
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