2exm: Difference between revisions

Revision as of 03:13, 4 May 2008

Human CDK2 in complex with isopentenyladenine

OverviewOverview

Cyclin-dependent kinases (CDKs) are conserved regulators of the eukaryotic cell cycle with different isoforms controlling specific phases of the cell cycle. Mitogenic or growth inhibitory signals are mediated, respectively, by activation or inhibition of CDKs which phosphorylate proteins associated with the cell cycle. The central role of CDKs in cell cycle regulation makes them a potential new target for inhibitory molecules with anti-proliferative and/or anti-neoplastic effects. We describe the crystal structures of the complexes of CDK2 with a weakly specific CDK inhibitor, N6-(delta 2-isopentenyl)adenine, and a strongly specific inhibitor, olomoucine. Both inhibitors are adenine derivatives and bind in the adenine binding pocket of CDK2, but in an unexpected and different orientation from the adenine of the authentic ligand ATP. The N6-benzyl substituent in olomoucine binds outside the conserved binding pocket and is most likely responsible for its specificity. The structural information from the CDK2-olomoucine complex will be useful in directing the search for the next generation inhibitors with improved properties.

About this StructureAbout this Structure

2EXM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Multiple modes of ligand recognition: crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine., Schulze-Gahmen U, Brandsen J, Jones HD, Morgan DO, Meijer L, Vesely J, Kim SH, Proteins. 1995 Aug;22(4):378-91. PMID:7479711 Page seeded by OCA on Sun May 4 03:13:51 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2exm.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_2exm", creates the "Structure Box" on the page.
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+You may change the PDB parameter (which sets the PDB file loaded into the applet)
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-|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= CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2exm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2exm OCA], [http://www.ebi.ac.uk/pdbsum/2exm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2exm RCSB]</span>
-}}
 '''Human CDK2 in complex with isopentenyladenine'''
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 [[Category: Single protein]]
 [[Category: Schulze-Gahmen, U.]]
-[[Category: ligand binding pocket between n-terminal and c-terminal domain]]
+[[Category: Ligand binding pocket between n-terminal and c-terminal domain]]
-[[Category: typical protein kinase fold]]
+[[Category: Typical protein kinase fold]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 03:13:51 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:55:08 2008''