2xjj

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{{STRUCTURE_2xjj| PDB=2xjj | SCENE= }}
 
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===Structure of HSP90 with small molecule inhibitor bound===
 
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{{ABSTRACT_PUBMED_20662534}}
 
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==Function==
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==Structure of HSP90 with small molecule inhibitor bound==
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[[http://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN]] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>
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<StructureSection load='2xjj' size='340' side='right'caption='[[2xjj]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2xjj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XJJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XJJ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L81:1,3-DIHYDROISOINDOL-2-YL-(6-HYDROXY-3,3-DIMETHYL-1,2-DIHYDROINDOL-5-YL)METHANONE'>L81</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xjj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xjj OCA], [https://pdbe.org/2xjj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xjj RCSB], [https://www.ebi.ac.uk/pdbsum/2xjj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xjj ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>
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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/xj/2xjj_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/main_output.php?pdb_ID=2xjj 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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Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d ) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man.
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==About this Structure==
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Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-di hydroisoindol-2-yl]methanone (AT13387), a Novel Inhibitor of the Molecular Chaperone Hsp90 by Fragment Based Drug Design.,Woodhead AJ, Angove H, Carr MG, Chessari G, Congreve M, Coyle JE, Cosme J, Graham B, Day PJ, Downham R, Fazal L, Feltell R, Figueroa E, Frederickson M, Lewis J, McMenamin R, Murray CW, O'Brien MA, Parra L, Patel S, Phillips T, Rees DC, Rich S, Smith DM, Trewartha G, Vinkovic M, Williams B, Woolford AJ J Med Chem. 2010 Jul 28. PMID:20662534<ref>PMID:20662534</ref>
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[[2xjj]] is a 2 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=2XJJ OCA].
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==See Also==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[Heat Shock Proteins|Heat Shock Proteins]]
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</div>
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<div class="pdbe-citations 2xjj" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:020662534</ref><references group="xtra"/><references/>
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*[[Heat Shock Protein structures|Heat Shock Protein structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Callaghan, O.]]
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[[Category: Large Structures]]
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[[Category: Carr, M G.]]
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[[Category: Callaghan O]]
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[[Category: Chessari, G.]]
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[[Category: Carr MG]]
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[[Category: Congreve, M.]]
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[[Category: Chessari G]]
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[[Category: Cowan, S.]]
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[[Category: Congreve M]]
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[[Category: Coyle, J E.]]
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[[Category: Cowan S]]
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[[Category: Downham, R.]]
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[[Category: Coyle JE]]
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[[Category: Figueroa, E.]]
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[[Category: Downham R]]
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[[Category: Frederickson, M.]]
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[[Category: Figueroa E]]
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[[Category: Graham, B.]]
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[[Category: Frederickson M]]
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[[Category: McMenamin, R.]]
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[[Category: Graham B]]
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[[Category: Murray, C W.]]
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[[Category: McMenamin R]]
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[[Category: OBrien, M A.]]
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[[Category: Murray CW]]
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[[Category: Patel, S.]]
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[[Category: OBrien MA]]
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[[Category: Phillips, T R.]]
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[[Category: Patel S]]
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[[Category: Williams, G.]]
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[[Category: Phillips TR]]
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[[Category: Woodhead, A J.]]
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[[Category: Williams G]]
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[[Category: Woolford, A J.A.]]
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[[Category: Woodhead AJ]]
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[[Category: Chaperone]]
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[[Category: Woolford AJA]]

Current revision

Structure of HSP90 with small molecule inhibitor bound

PDB ID 2xjj

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