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| {{STRUCTURE_1nvr| PDB=1nvr | SCENE= }} | | {{STRUCTURE_1nvr| PDB=1nvr | SCENE= }} |
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| '''The Complex Structure Of Checkpoint Kinase Chk1/Staurosporine'''
| | ===The Complex Structure Of Checkpoint Kinase Chk1/Staurosporine=== |
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| ==Overview==
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| Chk1 is a serine-threonine kinase that plays an important role in the DNA damage response, including G(2)/M cell cycle control. UCN-01 (7-hydroxystaurosporine), currently in clinical trials, has recently been shown to be a potent Chk1 inhibitor that abrogates the G(2)/M checkpoint induced by DNA-damaging agents. To understand the structural basis of Chk1 inhibition by UCN-01, we determined the crystal structure of the Chk1 kinase domain in complex with UCN-01. Chk1 structures with staurosporine and its analog SB-218078 were also determined. All three compounds bind in the ATP-binding pocket of Chk1, producing only slight changes in the protein conformation. Selectivity of UCN-01 toward Chk1 over cyclin-dependent kinases can be explained by the presence of a hydroxyl group in the lactam moiety interacting with the ATP-binding pocket. Hydrophobic interactions and hydrogen-bonding interactions were observed in the structures between UCN-01 and the Chk1 kinase domain. The high structural complementarity of these interactions is consistent with the potency and selectivity of UCN-01.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12244092}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12244092 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12244092}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Zhou, B B.]] | | [[Category: Zhou, B B.]] |
| [[Category: Chk1-staurosporine complex]] | | [[Category: Chk1-staurosporine complex]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:02:13 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:56:14 2008'' |