2wmq: Difference between revisions

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-[[Image:2wmq.png|left|200px]]
+==CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS==
+<StructureSection load='2wmq' size='340' side='right' caption='[[2wmq]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2wmq]] 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=2WMQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMQ FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZYQ:N-(4-OXO-5,6,7,8-TETRAHYDRO-4H-[1,3]THIAZOLO[5,4-C]AZEPIN-2-YL)ACETAMIDE'>ZYQ</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cgx|2cgx]], [[2bro|2bro]], [[2c3j|2c3j]], [[2brb|2brb]], [[2brh|2brh]], [[2cgv|2cgv]], [[2c3k|2c3k]], [[1nvr|1nvr]], [[2cgw|2cgw]], [[1zlt|1zlt]], [[2brn|2brn]], [[2ayp|2ayp]], [[1zys|1zys]], [[2cgu|2cgu]], [[1ia8|1ia8]], [[2br1|2br1]], [[2brg|2brg]], [[1nvs|1nvs]], [[2brm|2brm]], [[1nvq|1nvq]], [[2c3l|2c3l]], [[2wmt|2wmt]], [[2wmx|2wmx]], [[2wmv|2wmv]], [[2wms|2wms]], [[2wmw|2wmw]], [[2wmu|2wmu]], [[2wmr|2wmr]]</td></tr>
+<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>
+<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=2wmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wmq RCSB], [http://www.ebi.ac.uk/pdbsum/2wmq PDBsum]</span></td></tr>
+<table>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wm/2wmq_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Checkpoint kinase 1 (CHK1) is an oncology target of significant current interest. Inhibition of CHK1 abrogates DNA damage-induced cell cycle checkpoints and sensitizes p53 deficient cancer cells to genotoxic therapies. Using template screening, a fragment-based approach to small molecule hit generation, we have identified multiple CHK1 inhibitor scaffolds suitable for further optimization. The sequential combination of in silico low molecular weight template selection, a high concentration biochemical assay and hit validation through protein-ligand X-ray crystallography provided 13 template hits from an initial in silico screening library of ca. 15000 compounds. The use of appropriate counter-screening to rule out nonspecific aggregation by test compounds was essential for optimum performance of the high concentration bioassay. One low molecular weight, weakly active purine template hit was progressed by iterative structure-based design to give submicromolar pyrazolopyridines with good ligand efficiency and appropriate CHK1-mediated cellular activity in HT29 colon cancer cells.
-{{STRUCTURE_2wmq|  PDB=2wmq  |  SCENE=  }}
+Identification of inhibitors of checkpoint kinase 1 through template screening.,Matthews TP, Klair S, Burns S, Boxall K, Cherry M, Fisher M, Westwood IM, Walton MI, McHardy T, Cheung KM, Van Montfort R, Williams D, Aherne GW, Garrett MD, Reader J, Collins I J Med Chem. 2009 Aug 13;52(15):4810-9. PMID:19572549<ref>PMID:19572549</ref>
-===CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_19572549}}
-==About this Structure==
-[[2wmq]] 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=2WMQ OCA].
 ==See Also==
 *[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:019572549</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: Non-specific serine/threonine protein kinase]]