View source for 1uy6


==Human Hsp90-alpha with 9-Butyl-8-(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine==
<StructureSection load='1uy6' size='340' side='right'caption='[[1uy6]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1uy6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UY6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PU3:9-BUTYL-8-(3,4,5-TRIMETHOXYBENZYL)-9H-PURIN-6-AMINE'>PU3</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]], [[1uy7|1uy7]], [[1uy8|1uy8]], [[1uy9|1uy9]], [[1uyc|1uyc]], [[1uyd|1uyd]], [[1uye|1uye]], [[1uyf|1uyf]], [[1uyg|1uyg]], [[1uyh|1uyh]], [[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=1uy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uy6 OCA], [http://pdbe.org/1uy6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uy6 RCSB], [http://www.ebi.ac.uk/pdbsum/1uy6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1uy6 ProSAT]</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/uy/1uy6_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=1uy6 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibition 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<ref>PMID:15217611</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1uy6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Aherne, W]]
[[Category: Barril, X]]
[[Category: Beswick, M]]
[[Category: Boxall, K]]
[[Category: Collier, A]]
[[Category: Davies, N]]
[[Category: Drysdale, M]]
[[Category: Dymock, B]]
[[Category: Fink, A]]
[[Category: Fromont, C]]
[[Category: Hubbard, R E]]
[[Category: Massey, A]]
[[Category: Sharp, S]]
[[Category: Sheridan, L]]
[[Category: Surgenor, A]]
[[Category: Workman, P]]
[[Category: Wright, L]]
[[Category: Atp-binding]]
[[Category: Atpase]]
[[Category: Chaperone]]
[[Category: Heat shock]]
[[Category: Hsp90]]
[[Category: Pu3]]