6n8x

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Current revision (14:47, 13 March 2024) (edit) (undo)
 
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<StructureSection load='6n8x' size='340' side='right'caption='[[6n8x]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
<StructureSection load='6n8x' size='340' side='right'caption='[[6n8x]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6n8x]] 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=6N8X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N8X FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6n8x]] 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=6N8X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N8X FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KFY:9-[(2E)-but-2-en-1-yl]-8-[(3,4,5-trimethoxyphenyl)methyl]-9H-purin-6-amine'>KFY</scene></td></tr>
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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]] 1.4948448&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=KFY:9-[(2E)-but-2-en-1-yl]-8-[(3,4,5-trimethoxyphenyl)methyl]-9H-purin-6-amine'>KFY</scene></td></tr>
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<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=6n8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n8x OCA], [http://pdbe.org/6n8x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n8x RCSB], [http://www.ebi.ac.uk/pdbsum/6n8x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n8x ProSAT]</span></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=6n8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n8x OCA], [https://pdbe.org/6n8x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n8x RCSB], [https://www.ebi.ac.uk/pdbsum/6n8x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n8x ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://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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[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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Hsp90alpha and Hsp90beta are implicated in a number of cancers and neurodegenerative disorders but the lack of selective pharmacological probes confounds efforts to identify their individual roles. Here, we analyzed the binding of an Hsp90alpha-selective PU compound, PU-11-trans, to the two cytosolic paralogs. We determined the co-crystal structures of Hsp90alpha and Hsp90beta bound to PU-11-trans, as well as the structure of the apo Hsp90beta NTD. The two inhibitor-bound structures reveal that Ser52, a nonconserved residue in the ATP binding pocket in Hsp90alpha, provides additional stability to PU-11-trans through a water-mediated hydrogen-bonding network. Mutation of Ser52 to alanine, as found in Hsp90beta, alters the dissociation constant of Hsp90alpha for PU-11-trans to match that of Hsp90beta. Our results provide a structural explanation for the binding preference of PU inhibitors for Hsp90alpha and demonstrate that the single nonconserved residue in the ATP-binding pocket may be exploited for alpha/beta selectivity.
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Structures of Hsp90alpha and Hsp90beta bound to a purine-scaffold inhibitor reveal an exploitable residue for drug selectivity.,Huck JD, Que NLS, Sharma S, Taldone T, Chiosis G, Gewirth DT Proteins. 2019 May 29. doi: 10.1002/prot.25750. PMID:31141217<ref>PMID:31141217</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 6n8x" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Gewirth, D T]]
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[[Category: Gewirth DT]]
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[[Category: Huck, J D]]
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[[Category: Huck JD]]
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[[Category: Que, N L.S]]
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[[Category: Que NLS]]
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[[Category: Cancer]]
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[[Category: Chaperone]]
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[[Category: Chaperone-chaperone inhibitor complex]]
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[[Category: Cytosol]]
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[[Category: Hsp90]]
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[[Category: Inhibitor]]
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Current revision

Hsp90-alpha bound to PU-11-trans

PDB ID 6n8x

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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