2byh
From Proteopedia
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| - | [[Image:2byh.gif|left|200px]]<br /><applet load="2byh" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2byh, resolution 1.90Å" /> | ||
| - | '''3-(5-CHLORO-2,4-DIHYDROXYPHENYL)-PYRAZOLE-4-CARBOXAMIDES AS INHIBITORS OF THE HSP90 MOLECULAR CHAPERONE'''<br /> | ||
| - | == | + | ==3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as Inhibitors of the Hsp90 Molecular Chaperone== |
| - | Information from X-ray crystal structures of Hsp90 inhibitors bound to the | + | <StructureSection load='2byh' size='340' side='right'caption='[[2byh]], [[Resolution|resolution]] 1.90Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2byh]] is a 1 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=2BYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BYH FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2D7:N-(4-ACETYLPHENYL)-5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE'>2D7</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2byh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2byh OCA], [https://pdbe.org/2byh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2byh RCSB], [https://www.ebi.ac.uk/pdbsum/2byh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2byh ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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> | ||
| + | == 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/by/2byh_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/main_output.php?pdb_ID=2byh ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction. | ||
| - | + | 3-(5-Chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone.,Brough PA, Barril X, Beswick M, Dymock BW, Drysdale MJ, Wright L, Grant K, Massey A, Surgenor A, Workman P Bioorg Med Chem Lett. 2005 Dec 1;15(23):5197-201. Epub 2005 Oct 5. PMID:16213716<ref>PMID:16213716</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2byh" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Barril X]] | ||
| + | [[Category: Beswick M]] | ||
| + | [[Category: Brough PA]] | ||
| + | [[Category: Drysdale MJ]] | ||
| + | [[Category: Dymock BW]] | ||
| + | [[Category: Grant K]] | ||
| + | [[Category: Massey A]] | ||
| + | [[Category: Surgenor A]] | ||
| + | [[Category: Workman P]] | ||
| + | [[Category: Wright L]] | ||
Current revision
3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as Inhibitors of the Hsp90 Molecular Chaperone
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Categories: Homo sapiens | Large Structures | Barril X | Beswick M | Brough PA | Drysdale MJ | Dymock BW | Grant K | Massey A | Surgenor A | Workman P | Wright L
