6n8w
From Proteopedia
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<StructureSection load='6n8w' size='340' side='right'caption='[[6n8w]], [[Resolution|resolution]] 3.09Å' scene=''> | <StructureSection load='6n8w' size='340' side='right'caption='[[6n8w]], [[Resolution|resolution]] 3.09Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6n8w]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N8W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N8W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n8w]] is a 4 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=6N8W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N8W FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AB1, HSP90B, HSPC2, HSPCB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6n8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n8w OCA], [http://pdbe.org/6n8w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n8w RCSB], [http://www.ebi.ac.uk/pdbsum/6n8w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n8w ProSAT]</span></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=6n8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n8w OCA], [http://pdbe.org/6n8w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n8w RCSB], [http://www.ebi.ac.uk/pdbsum/6n8w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n8w ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://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> | [[http://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. | ||
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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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6n8w" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gewirth, D T]] | [[Category: Gewirth, D T]] | ||
Revision as of 06:28, 10 July 2019
Structure of Unliganded Hsp90-Beta N-Terminal Domain
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Categories: Human | Large Structures | Gewirth, D T | Huck, J D | Que, N L.S | Chaperone | Cytosolic | Heat-shock | Hsp90
