| pubmed-article:12244092 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12244092 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:12244092 | lifeskim:mentions | umls-concept:C1332753 | lld:lifeskim |
| pubmed-article:12244092 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:12244092 | lifeskim:mentions | umls-concept:C0678594 | lld:lifeskim |
| pubmed-article:12244092 | lifeskim:mentions | umls-concept:C1527178 | lld:lifeskim |
| pubmed-article:12244092 | lifeskim:mentions | umls-concept:C0950721 | lld:lifeskim |
| pubmed-article:12244092 | pubmed:dateCreated | 2002-11-26 | lld:pubmed |
| pubmed-article:12244092 | pubmed:abstractText | 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. | lld:pubmed |
| pubmed-article:12244092 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12244092 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:12244092 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:DavisStephen... | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:ZhouBin-Bing... | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:ZhaoHuizhenH | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:ZhaoBaoguangB | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:BowerMichael... | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:McDevittPatri... | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:JohansonKyung... | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:GreenSusan... | lld:pubmed |
| pubmed-article:12244092 | pubmed:author | pubmed-author:ConchaNestor... | lld:pubmed |
| pubmed-article:12244092 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12244092 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12244092 | pubmed:pagination | 46609-15 | lld:pubmed |
| pubmed-article:12244092 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
| pubmed-article:12244092 | pubmed:articleTitle | Structural basis for Chk1 inhibition by UCN-01. | lld:pubmed |
| pubmed-article:12244092 | pubmed:affiliation | Department of Structural Biology, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA. | lld:pubmed |
| entrez-gene:1111 | entrezgene:pubmed | pubmed-article:12244092 | lld:entrezgene |
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