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2h55

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{{Seed}}
 
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[[Image:2h55.png|left|200px]]
 
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==Structure of human Hsp90-alpha bound to the potent water soluble inhibitor PU-DZ8==
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The line below this paragraph, containing "STRUCTURE_2h55", creates the "Structure Box" on the page.
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<StructureSection load='2h55' size='340' side='right'caption='[[2h55]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2h55]] 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=2H55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H55 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&#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=DZ8:2-FLUORO-8-[(6-IODO-1,3-BENZODIOXOL-5-YL)METHYL]-9-[3-(ISOPROPYLAMINO)PROPYL]-9H-PURIN-6-AMINE'>DZ8</scene></td></tr>
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{{STRUCTURE_2h55| PDB=2h55 | SCENE= }}
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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=2h55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h55 OCA], [https://pdbe.org/2h55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h55 RCSB], [https://www.ebi.ac.uk/pdbsum/2h55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h55 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/h5/2h55_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=2h55 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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Hsp90 chaperones play a critical role in modulating the activity of many cell signaling proteins and are an attractive target for anti-cancer therapeutics. We report here the structures of the water soluble 8-aryl-sulfanyl adenine class Hsp90 inhibitors, 1 (PU-H71) and 2 (PU-H64), in complex with the N-terminal domain of human Hsp90alpha. The conformation of 1 when bound to Hsp90 differs from previously reported 8-aryl adenine Hsp90 inhibitors including 3 (PU24FCl). While the binding mode for 3 places the 2'-halide of the 8-aryl group on top of the adenine ring, for 1 and 2, we show that the 2'-halide is rotated approximately 180 degrees away. This difference explains the opposing trends in Hsp90 inhibitory activity for the 2'-halo derivatives of the 3',4',5'-trimethoxy series where Cl &gt; Br &gt; I compared to the 4',5'-methylenedioxy series where I &gt; Br &gt; Cl. We also present quantum chemical calculations of 2 and its analogues that illuminate their basis for Hsp90 inhibition. The calculated conformation of 2 agreed well with the crystallographically observed conformations of 1 and 2. The predictive nature of the calculations has allowed the exploration of additional derivatives based on the 8-aryl adenine scaffold.
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===Structure of human Hsp90-alpha bound to the potent water soluble inhibitor PU-DZ8===
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Structural and quantum chemical studies of 8-aryl-sulfanyl adenine class Hsp90 inhibitors.,Immormino RM, Kang Y, Chiosis G, Gewirth DT J Med Chem. 2006 Aug 10;49(16):4953-60. PMID:16884307<ref>PMID:16884307</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2h55" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_16884307}}, adds the Publication Abstract to the page
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*[[Heat Shock Protein structures|Heat Shock Protein structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 16884307 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16884307}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2H55 is a 1 chain structure of 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=2H55 OCA].
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==Reference==
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<ref group="xtra">PMID:16884307</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Gewirth, D T.]]
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[[Category: Large Structures]]
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[[Category: Immormino, R M.]]
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[[Category: Gewirth DT]]
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[[Category: Chaperone]]
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[[Category: Immormino RM]]
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[[Category: Dz8]]
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[[Category: Grp94]]
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[[Category: H64]]
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[[Category: H71]]
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[[Category: Hsp90]]
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[[Category: Pu3]]
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[[Category: Purine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 14:13:10 2009''
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Current revision

Structure of human Hsp90-alpha bound to the potent water soluble inhibitor PU-DZ8

PDB ID 2h55

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