1uyh: Difference between revisions
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==Human Hsp90-alpha with 9-Butyl-8-(2,5-dimethoxy-benzyl)-2-fluoro-9H-purin-6-ylamine== | |||
<StructureSection load='1uyh' size='340' side='right' caption='[[1uyh]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='1uyh' size='340' side='right' caption='[[1uyh]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PU0:9-BUTYL-8-(2,5-DIMETHOXY-BENZYL)-2-FLUORO-9H-PURIN-6-YLAMINE'>PU0</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PU0:9-BUTYL-8-(2,5-DIMETHOXY-BENZYL)-2-FLUORO-9H-PURIN-6-YLAMINE'>PU0</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1byq|1byq]], [[1osf|1osf]], [[1yer|1yer]], [[1yes|1yes]], [[1yet|1yet]], [[1uy6|1uy6]], [[1uy7|1uy7]], [[1uy8|1uy8]], [[1uy9|1uy9]], [[1uyc|1uyc]], [[1uyd|1uyd]], [[1uye|1uye]], [[1uyf|1uyf]], [[1uyg|1uyg]], [[1uyi|1uyi]], [[1uyk|1uyk]], [[1uyl|1uyl]], [[1uym|1uym]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1byq|1byq]], [[1osf|1osf]], [[1yer|1yer]], [[1yes|1yes]], [[1yet|1yet]], [[1uy6|1uy6]], [[1uy7|1uy7]], [[1uy8|1uy8]], [[1uy9|1uy9]], [[1uyc|1uyc]], [[1uyd|1uyd]], [[1uye|1uye]], [[1uyf|1uyf]], [[1uyg|1uyg]], [[1uyi|1uyi]], [[1uyk|1uyk]], [[1uyl|1uyl]], [[1uym|1uym]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uyh OCA], [http://pdbe.org/1uyh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uyh RCSB], [http://www.ebi.ac.uk/pdbsum/1uyh PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uyh OCA], [http://pdbe.org/1uyh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uyh RCSB], [http://www.ebi.ac.uk/pdbsum/1uyh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1uyh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=1uyh ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 1uyh" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1uyh" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 10:09, 16 November 2017
Human Hsp90-alpha with 9-Butyl-8-(2,5-dimethoxy-benzyl)-2-fluoro-9H-purin-6-ylamineHuman Hsp90-alpha with 9-Butyl-8-(2,5-dimethoxy-benzyl)-2-fluoro-9H-purin-6-ylamine
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInhibition of the ATPase activity of the chaperone protein HSP90 is a potential strategy for treatment of cancers. We have determined structures of the HSP90alpha N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays. The compounds induce upregulation of HSP70 and downregulation of the known HSP90 client proteins Raf-1, CDK4, and ErbB2, confirming that the molecules inhibit cell growth by a mechanism dependent on HSP90 inhibition. We have also determined the first structure of the N-terminal domain of HSP90beta, complexed with PU3. The structures allow a detailed rationale to be developed for the observed affinity of the PU3 class of compounds for HSP90 and also provide a structural framework for design of compounds with improved binding affinity and drug-like properties. Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms.,Wright L, Barril X, Dymock B, Sheridan L, Surgenor A, Beswick M, Drysdale M, Collier A, Massey A, Davies N, Fink A, Fromont C, Aherne W, Boxall K, Sharp S, Workman P, Hubbard RE Chem Biol. 2004 Jun;11(6):775-85. PMID:15217611[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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