2hy0

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[[Image:2hy0.png|left|200px]]
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==crystal structure of chek1 in complex with inhibitor 22==
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<StructureSection load='2hy0' size='340' side='right' caption='[[2hy0]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2hy0]] is a 1 chain structure with 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=2HY0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HY0 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=306:3-[5-(PIPERIDIN-1-YLMETHYL)-1H-INDOL-2-YL]-6-(1H-PYRAZOL-4-YL)QUINOLIN-2(1H)-ONE'>306</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hxl|2hxl]], [[2hxq|2hxq]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHEK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hy0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hy0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hy0 RCSB], [http://www.ebi.ac.uk/pdbsum/2hy0 PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hy/2hy0_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Through a comparison of X-ray co-crystallographic data for 1 and 2 in the Chek1 active site, it was hypothesized that the affinity of the indolylquinolinone series (2) for Chek1 kinase would be improved via C6 substitution into the hydrophobic region I (HI) pocket. An efficient route to 6-bromo-3-indolyl-quinolinone (9) was developed, and this series was rapidly optimized for potency by modification at C6. A general trend was observed among these low nanomolar Chek1 inhibitors that compounds with multiple basic amines, or elevated polar surface area (PSA) exhibited poor cell potency. Minimization of these parameters (basic amines, PSA) resulted in Chek1 inhibitors with improved cell potency, and preliminary pharmacokinetic data are presented for several of these compounds.
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{{STRUCTURE_2hy0| PDB=2hy0 | SCENE= }}
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Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors.,Huang S, Garbaccio RM, Fraley ME, Steen J, Kreatsoulas C, Hartman G, Stirdivant S, Drakas B, Rickert K, Walsh E, Hamilton K, Buser CA, Hardwick J, Mao X, Abrams M, Beck S, Tao W, Lobell R, Sepp-Lorenzino L, Yan Y, Ikuta M, Murphy JZ, Sardana V, Munshi S, Kuo L, Reilly M, Mahan E Bioorg Med Chem Lett. 2006 Nov 15;16(22):5907-12. Epub 2006 Sep 20. PMID:16990002<ref>PMID:16990002</ref>
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===crystal structure of chek1 in complex with inhibitor 22===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_16990002}}
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==About this Structure==
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[[2hy0]] is a 1 chain structure with 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=2HY0 OCA].
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==See Also==
==See Also==
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:016990002</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]

Revision as of 03:12, 29 September 2014

crystal structure of chek1 in complex with inhibitor 22

2hy0, resolution 1.70Å

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