1uym

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[[Image:1uym.gif|left|200px]]<br /><applet load="1uym" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1uym, resolution 2.45&Aring;" />
 
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'''HUMAN HSP90-BETA WITH PU3 (9-BUTYL-8(3,4,5-TRIMETHOXY-BENZYL)-9H-PURIN-6-YLAMINE)'''<br />
 
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==Overview==
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==Human Hsp90-beta with PU3 (9-Butyl-8(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine)==
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<StructureSection load='1uym' size='340' side='right'caption='[[1uym]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1uym]] 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=1UYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UYM 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]] 2.45&#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=PU3:9-BUTYL-8-(3,4,5-TRIMETHOXYBENZYL)-9H-PURIN-6-AMINE'>PU3</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=1uym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uym OCA], [https://pdbe.org/1uym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uym RCSB], [https://www.ebi.ac.uk/pdbsum/1uym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uym ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HS90B_HUMAN HS90B_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:16478993</ref> <ref>PMID:19696785</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/uy/1uym_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=1uym 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 ==
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.
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.
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==About this Structure==
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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>
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1UYM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PU3:'>PU3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Pu3+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UYM OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15217611 15217611]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 1uym" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Aherne, W.]]
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[[Category: Barril, X.]]
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[[Category: Beswick, M.]]
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[[Category: Boxall, K.]]
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[[Category: Collier, A.]]
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[[Category: Davies, N.]]
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[[Category: Drysdale, M.]]
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[[Category: Dymock, B.]]
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[[Category: Fink, A.]]
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[[Category: Fromont, C.]]
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[[Category: Hubbard, R E.]]
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[[Category: Massey, A.]]
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[[Category: Sharp, S.]]
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[[Category: Sheridan, L.]]
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[[Category: Surgenor, A.]]
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[[Category: Workman, P.]]
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[[Category: Wright, L.]]
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[[Category: PU3]]
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[[Category: atp-binding]]
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[[Category: atpase]]
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[[Category: chaperone]]
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[[Category: heat shock]]
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[[Category: hsp90]]
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[[Category: pu3]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:29:45 2008''
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==See Also==
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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>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Aherne W]]
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[[Category: Barril X]]
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[[Category: Beswick M]]
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[[Category: Boxall K]]
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[[Category: Collier A]]
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[[Category: Davies N]]
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[[Category: Drysdale M]]
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[[Category: Dymock B]]
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[[Category: Fink A]]
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[[Category: Fromont C]]
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[[Category: Hubbard RE]]
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[[Category: Massey A]]
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[[Category: Sharp S]]
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[[Category: Sheridan L]]
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[[Category: Surgenor A]]
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[[Category: Workman P]]
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[[Category: Wright L]]

Current revision

Human Hsp90-beta with PU3 (9-Butyl-8(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine)

PDB ID 1uym

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