3o2f: Difference between revisions
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==Structure of the N-domain of GRP94 bound to the HSP90 inhibitor PU-H54== | |||
<StructureSection load='3o2f' size='340' side='right' caption='[[3o2f]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3o2f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Canfa Canfa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O2F 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>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=P54:8-[(2,4-DIMETHYLPHENYL)SULFANYL]-3-PENT-4-YN-1-YL-3H-PURIN-6-AMINE'>P54</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fwy|2fwy]], [[3o0i|3o0i]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRP94, HSP90B1, TRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9615 CANFA])</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=3o2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o2f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o2f RCSB], [http://www.ebi.ac.uk/pdbsum/3o2f PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/ENPL_CANFA ENPL_CANFA]] Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors. Functions in endoplasmic reticulum associated degradation (ERAD). Has ATPase activity (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Although the Hsp90 chaperone family, comprised in humans of four paralogs, Hsp90alpha, Hsp90beta, Grp94 and Trap-1, has important roles in malignancy, the contribution of each paralog to the cancer phenotype is poorly understood. This is in large part because reagents to study paralog-specific functions in cancer cells have been unavailable. Here we combine compound library screening with structural and computational analyses to identify purine-based chemical tools that are specific for Hsp90 paralogs. We show that Grp94 selectivity is due to the insertion of these compounds into a new allosteric pocket. We use these tools to demonstrate that cancer cells use individual Hsp90 paralogs to regulate a client protein in a tumor-specific manner and in response to proteome alterations. Finally, we provide new mechanistic evidence explaining why selective Grp94 inhibition is particularly efficacious in certain breast cancers. | |||
Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2.,Patel PD, Yan P, Seidler PM, Patel HJ, Sun W, Yang C, Que NS, Taldone T, Finotti P, Stephani RA, Gewirth DT, Chiosis G Nat Chem Biol. 2013 Sep 1. doi: 10.1038/nchembio.1335. PMID:23995768<ref>PMID:23995768</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Endoplasmin|Endoplasmin]] | *[[Endoplasmin|Endoplasmin]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Canfa]] | [[Category: Canfa]] | ||
[[Category: Gewirth, D T | [[Category: Gewirth, D T]] | ||
[[Category: Seidler, P M | [[Category: Seidler, P M]] | ||
[[Category: Chaperone-inhibitor complex]] | [[Category: Chaperone-inhibitor complex]] | ||
[[Category: Hsp90 heat-shock protein]] | [[Category: Hsp90 heat-shock protein]] | ||