2a4l

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{{STRUCTURE_2a4l| PDB=2a4l | SCENE= }}
{{STRUCTURE_2a4l| PDB=2a4l | SCENE= }}
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'''Human cyclin-dependent kinase 2 in complex with roscovitine'''
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===Human cyclin-dependent kinase 2 in complex with roscovitine===
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==Overview==
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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. &amp; 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.
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{{ABSTRACT_PUBMED_9030780}}
==About this Structure==
==About this Structure==
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==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/9030780 9030780]
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:[http://www.ncbi.nlm.nih.gov/pubmed/9030780 9030780]
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Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase., De Azevedo WF Jr, Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH, Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2735-40. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8610110 8610110]
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Crystal structure of cyclin-dependent kinase 2., De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH, Nature. 1993 Jun 17;363(6430):595-602. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8510751 8510751]
[[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: Serine/threonine protein kinase]]
[[Category: Serine/threonine protein kinase]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 08:56:49 2008''

Revision as of 05:56, 28 July 2008

Image:2a4l.png

Template:STRUCTURE 2a4l

Human cyclin-dependent kinase 2 in complex with roscovitine

Template:ABSTRACT PUBMED 9030780

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

Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase., De Azevedo WF Jr, Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH, Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2735-40. PMID:8610110

Crystal structure of cyclin-dependent kinase 2., De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH, Nature. 1993 Jun 17;363(6430):595-602. PMID:8510751

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