2a4l
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=RRC:R-ROSCOVITINE'>RRC</scene> | |LIGAND= <scene name='pdbligand=RRC:R-ROSCOVITINE'>RRC</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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1hck|1HCK]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a4l OCA], [http://www.ebi.ac.uk/pdbsum/2a4l PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a4l RCSB]</span> | ||
}} | }} | ||
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[[Category: Jr., W F.De Azevedo.]] | [[Category: Jr., W F.De Azevedo.]] | ||
[[Category: Kim, S H.]] | [[Category: Kim, S H.]] | ||
| - | [[Category: RRC]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: cell cycle]] | [[Category: cell cycle]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:47:46 2008'' |
Revision as of 22:47, 30 March 2008
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| , resolution 2.4Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 1HCK
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human cyclin-dependent kinase 2 in complex with roscovitine
Overview
Cyclin-dependent kinases (cdk) control the cell division cycle (cdc). These kinases and their regulators are frequently deregulated in human tumours. A potent inhibitor of cdks, roscovitine [2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurin e], was identified by screening a series of C2,N6,N9-substituted adenines on purified cdc2/cyclin B. Roscovitine displays high efficiency and high selectivity (Meijer, L., Borgne, A., Mulner, O., Chong, J. P. J., Blow, J. J., Inagaki, N., Inagaki, M., Delcros, J.-G. & Moulinoux, J.-P. (1997) Eur. J. Biochem. 243, 527-536). It behaves as a competitive inhibitor for ATP binding to cdc2. We determined the crystal structure of a complex between cdk2 and roscovitine at 0.24-nm (2.4 A) resolution and refined to an Rfactor of 0.18. The purine portion of the inhibitor binds to the adenine binding pocket of cdk2. The position of the benzyl ring group of the inhibitor enables the inhibitor to make contacts with the enzyme not observed in the ATP-complex structure. Analysis of the position of this benzyl ring explains the specificity of roscovitine in inhibiting cdk2. The structure also reveals that the (R)-stereoisomer of roscovitine is bound to cdk2. The (R)-isomer is about twice as potent in inhibiting cdc2/cyclin B than the (S)-isomer. Results from structure/activity studies and from analysis of the cdk2/roscovitine complex crystal structure should allow the design of even more potent cdk inhibitors.
About this Structure
2A4L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine., De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH, Eur J Biochem. 1997 Jan 15;243(1-2):518-26. PMID:9030780
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