2euf: Difference between revisions
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[[Image:2euf.gif|left|200px]] | [[Image:2euf.gif|left|200px]] | ||
'''X-ray structure of human CDK6-Vcyclin in complex with the inhibitor PD0332991''' | {{Structure | ||
|PDB= 2euf |SIZE=350|CAPTION= <scene name='initialview01'>2euf</scene>, resolution 3.00Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=LQQ:6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-[(5-PIPERAZIN-1-YLPYRIDIN-2-YL)AMINO]PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE'>LQQ</scene> and <scene name='pdbligand=DMS:DIMETHYL SULFOXIDE'>DMS</scene> | |||
|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= 72, ECLF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=134392 Saimiriine Herpesvirus 3]), CDK6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''X-ray structure of human CDK6-Vcyclin in complex with the inhibitor PD0332991''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
2EUF is a [ | 2EUF is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Saimiriine_herpesvirus_3 Saimiriine herpesvirus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EUF OCA]. | ||
==Reference== | ==Reference== | ||
Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition., Lu H, Schulze-Gahmen U, J Med Chem. 2006 Jun 29;49(13):3826-31. PMID:[http:// | Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition., Lu H, Schulze-Gahmen U, J Med Chem. 2006 Jun 29;49(13):3826-31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16789739 16789739] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
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[[Category: inhibitor complex of human cyclin-dependent kinase 6]] | [[Category: inhibitor complex of human cyclin-dependent kinase 6]] | ||
''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 16:44:30 2008'' | ||
Revision as of 17:44, 20 March 2008
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| , resolution 3.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | 72, ECLF2 (Saimiriine Herpesvirus 3), CDK6 (Homo sapiens) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-ray structure of human CDK6-Vcyclin in complex with the inhibitor PD0332991
OverviewOverview
Cyclin-dependent kinases (CDKs) are key players in cell cycle control, and genetic alterations of CDKs and their regulators have been linked to a variety of cancers. Hence, CDKs are obvious targets for therapeutic intervention in various proliferative diseases, including cancer. To date, drug design efforts have mostly focused on CDK2 because methods for crystallization of its inhibitor complexes have been well established. CDK4 and CDK6, however, may be at least as important as enzymes for cell cycle regulation and could provide alternative treatment options. We describe here two complex structures of human CDK6 with a very specific kinase inhibitor, PD0332991, which is based on a pyrido[2,3-d]pyrimidin-7-one scaffold, and with the less specific aminopurvalanol inhibitor. Analysis of the structures suggests that relatively small conformational differences between CDK2 and CDK6 in the hinge region are contributing to the inhibitor specificity by inducing changes in the inhibitor orientation that lead to sterical clashes in CDK2 but not CDK6. These complex structures provide valuable insights for the future development of CDK-specific inhibitors.
About this StructureAbout this Structure
2EUF is a Protein complex structure of sequences from Homo sapiens and Saimiriine herpesvirus 3. Full crystallographic information is available from OCA.
ReferenceReference
Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition., Lu H, Schulze-Gahmen U, J Med Chem. 2006 Jun 29;49(13):3826-31. PMID:16789739
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