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1nvs

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(New page: 200px<br /> <applet load="1nvs" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nvs, resolution 1.8&Aring;" /> '''The Complex Structur...)
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'''The Complex Structure Of Checkpoint Kinase Chk1/SB218078'''<br />
'''The Complex Structure Of Checkpoint Kinase Chk1/SB218078'''<br />
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==About this Structure==
==About this Structure==
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1NVS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and UCM as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NVS OCA].
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1NVS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=UCM:'>UCM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NVS OCA].
==Reference==
==Reference==
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[[Category: chk1-sb218078 complex]]
[[Category: chk1-sb218078 complex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:26:18 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:31:10 2008''

Revision as of 14:31, 15 February 2008


1nvs, resolution 1.8Å

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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 with and as ligands. 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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