2euf: Difference between revisions

Revision as of 03:07, 4 May 2008

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 2. 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 Page seeded by OCA on Sun May 4 03:07:37 2008

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OCA

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 [[Image:2euf.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_2euf", creates the "Structure Box" on the page.
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+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= 72, ECLF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10381 Saimiriine herpesvirus 2]), CDK6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2euf|  PDB=2euf  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2euf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2euf OCA], [http://www.ebi.ac.uk/pdbsum/2euf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2euf RCSB]</span>
-}}
 '''X-ray structure of human CDK6-Vcyclin in complex with the inhibitor PD0332991'''
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 [[Category: Lu, H.]]
 [[Category: Schulze-Gahmen, U.]]
-[[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 Sun May  4 03:07:37 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:53:55 2008''