1nvs: Difference between revisions
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[[Image:1nvs.jpg|left|200px]] | [[Image:1nvs.jpg|left|200px]] | ||
'''The Complex Structure Of Checkpoint Kinase Chk1/SB218078''' | {{Structure | ||
|PDB= 1nvs |SIZE=350|CAPTION= <scene name='initialview01'>1nvs</scene>, resolution 1.8Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=UCM:REL-(9R,12S)-9,10,11,12-TETRAHYDRO-9,12-EPOXY-1H-DIINDOLO[1,2,3-FG:3',2',1'-KL]PYRROLO[3,4-I][1,6]BENZODIAZOCINE-1,3(2H)-DIONE'>UCM</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''The Complex Structure Of Checkpoint Kinase Chk1/SB218078''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1NVS is a [ | 1NVS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NVS OCA]. | ||
==Reference== | ==Reference== | ||
Structural basis for Chk1 inhibition by UCN-01., Zhao B, Bower MJ, McDevitt PJ, Zhao H, Davis ST, Johanson KO, Green SM, Concha NO, Zhou BB, J Biol Chem. 2002 Nov 29;277(48):46609-15. Epub 2002 Sep 19. PMID:[http:// | Structural basis for Chk1 inhibition by UCN-01., Zhao B, Bower MJ, McDevitt PJ, Zhao H, Davis ST, Johanson KO, Green SM, Concha NO, Zhou BB, J Biol Chem. 2002 Nov 29;277(48):46609-15. Epub 2002 Sep 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12244092 12244092] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: chk1-sb218078 complex]] | [[Category: chk1-sb218078 complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:02:21 2008'' | ||
Revision as of 11:02, 20 March 2008
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| 1nvs, resolution 1.8Å | |||||||||||||
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| Ligands: | SO4 and UCM | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
The Complex Structure Of Checkpoint Kinase Chk1/SB218078
Overview
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.
About this Structure
1NVS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for Chk1 inhibition by UCN-01., Zhao B, Bower MJ, McDevitt PJ, Zhao H, Davis ST, Johanson KO, Green SM, Concha NO, Zhou BB, J Biol Chem. 2002 Nov 29;277(48):46609-15. Epub 2002 Sep 19. PMID:12244092
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