6n8y
From Proteopedia
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(New page: '''Unreleased structure''' The entry 6n8y is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Hsp90-beta bound to PU-11-trans== | |
| + | <StructureSection load='6n8y' size='340' side='right'caption='[[6n8y]], [[Resolution|resolution]] 1.55Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6n8y]] 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=6N8Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N8Y FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.553908Å</td></tr> | ||
| + | <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> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6n8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n8y OCA], [https://pdbe.org/6n8y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n8y RCSB], [https://www.ebi.ac.uk/pdbsum/6n8y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n8y ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6n8y" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gewirth DT]] | ||
| + | [[Category: Huck JD]] | ||
| + | [[Category: Que NLS]] | ||
Current revision
Hsp90-beta bound to PU-11-trans
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