6gfa - Revision history

OCA at 07:13, 16 October 2019

2019-10-16T07:13:47Z

←Older revision		Revision as of 07:13, 16 October 2019
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	</div>		</div>
	<div class="pdbe-citations 6gfa" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6gfa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Heat Shock Protein structures\|Heat Shock Protein structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:45, 3 July 2019

2019-07-03T06:45:50Z

←Older revision		Revision as of 06:45, 3 July 2019
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	<StructureSection load='6gfa' size='340' side='right'caption='[[6gfa]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6gfa' size='340' side='right'caption='[[6gfa]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gfa]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GFA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GFA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gfa]] 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=6GFA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GFA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HSPH1, HSP105, HSP110, KIAA0201 ([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=6gfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gfa OCA], [http://pdbe.org/6gfa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gfa RCSB], [http://www.ebi.ac.uk/pdbsum/6gfa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gfa 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=6gfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gfa OCA], [http://pdbe.org/6gfa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gfa RCSB], [http://www.ebi.ac.uk/pdbsum/6gfa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gfa ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/HS105_HUMAN HS105_HUMAN]] Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity).[UniProtKB:Q60446][UniProtKB:Q61699]<ref>PMID:24318877</ref>		[[http://www.uniprot.org/uniprot/HS105_HUMAN HS105_HUMAN]] Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity).[UniProtKB:Q60446][UniProtKB:Q61699]<ref>PMID:24318877</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pro-survival stress-inducible chaperone HSP110 is the only HSP for which a mutation has been found in a cancer. Multicenter clinical studies demonstrated a direct association between HSP110 inactivating mutation presence and excellent prognosis in colorectal cancer patients. Here, we have combined crystallographic studies on human HSP110 and in silico modeling to identify HSP110 inhibitors that could be used in colorectal cancer therapy. Two molecules (foldamers 33 and 52), binding to the same cleft of HSP110 nucleotide-binding domain, were selected from a chemical library (by co-immunoprecipitation, AlphaScreening, Interference-Biolayer, Duo-link). These molecules block HSP110 chaperone anti-aggregation activity and HSP110 association to its client protein STAT3, thereby inhibiting STAT3 phosphorylation and colorectal cancer cell growth. These effects were strongly decreased in HSP110 knockdown cells. Foldamer's 33 ability to inhibit tumor growth was confirmed in two colorectal cancer animal models. Although tumor cell death (apoptosis) was noted after treatment of the animals with foldamer 33, no apparent toxicity was observed, notably in epithelial cells from intestinal crypts. Taken together, we identified the first HSP110 inhibitor, a possible drug-candidate for colorectal cancer patients whose unfavorable outcome is associated to HSP110.
		+
		+	Selecting the first chemical molecule inhibitor of HSP110 for colorectal cancer therapy.,Gozzi GJ, Gonzalez D, Boudesco C, Dias AMM, Gotthard G, Uyanik B, Dondaine L, Marcion G, Hermetet F, Denis C, Hardy L, Suzanne P, Douhard R, Jego G, Dubrez L, Demidov ON, Neiers F, Briand L, Sopkova-de Oliveira Santos J, Voisin-Chiret AS, Garrido C Cell Death Differ. 2019 May 8. pii: 10.1038/s41418-019-0343-4. doi:, 10.1038/s41418-019-0343-4. PMID:31068676<ref>PMID:31068676</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6gfa" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Briand, L]]		[[Category: Briand, L]]

OCA at 11:16, 10 May 2019

2019-05-10T11:16:49Z

←Older revision		Revision as of 11:16, 10 May 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6gfa ~~is ON HOLD~~	+	==Structure of Nucleotide binding domain of HSP110, ATP and Mg2+ complexed==
-		+	<StructureSection load='6gfa' size='340' side='right'caption='[[6gfa]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~: ~~Gonzalez, D~~.~~, Gotthard, G~~., ~~Gozzi~~, G.J.~~, Seigneuric, R~~., ~~Neiers~~, F., ~~Briand, L~~., ~~Garrido, C~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6gfa]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GFA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GFA FirstGlance]. <br>
-	~~Description~~: ~~Structure~~ of ~~Nucleotide binding domain~~ of ~~HSP110~~, ATP and ~~Mg2+ complexed~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6gfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gfa OCA], [http://pdbe.org/6gfa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gfa RCSB], [http://www.ebi.ac.uk/pdbsum/6gfa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gfa ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HS105_HUMAN HS105_HUMAN]] Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity).[UniProtKB:Q60446][UniProtKB:Q61699]<ref>PMID:24318877</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Briand, L]]
		+	[[Category: Garrido, C]]
		+	[[Category: Gonzalez, D]]
	[[Category: Gotthard, G]]		[[Category: Gotthard, G]]
-	[[Category: ~~Gonzalez~~, D]]	+	[[Category: Gozzi, G J]]
	[[Category: Neiers, F]]		[[Category: Neiers, F]]
-	[[Category: Briand, L]]
-	[[Category: Gozzi, G.J]]
	[[Category: Seigneuric, R]]		[[Category: Seigneuric, R]]
-	[[Category: ~~Garrido, C~~]]	+	[[Category: Chaperone]]
		+	[[Category: Hsp105]]
		+	[[Category: Hsp110]]
		+	[[Category: Hsp110de9]]
		+	[[Category: Hsph1]]
		+	[[Category: Nucleotide-binding domain]]

OCA: Protected "6gfa" [edit=sysop:move=sysop]

2018-05-09T05:05:12Z

Protected "6gfa" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:05, 9 May 2018

OCA: New page: '''Unreleased structure''' The entry 6gfa is ON HOLD Authors: Gonzalez, D., Gotthard, G., Gozzi, G.J., Seigneuric, R., Neiers, F., Briand, L., Garrido, C. Description: Structure of Nuc...

2018-05-09T05:05:11Z

New page: '''Unreleased structure''' The entry 6gfa is ON HOLD Authors: Gonzalez, D., Gotthard, G., Gozzi, G.J., Seigneuric, R., Neiers, F., Briand, L., Garrido, C. Description: Structure of Nuc...

New page

'''Unreleased structure'''

The entry 6gfa is ON HOLD

Authors: Gonzalez, D., Gotthard, G., Gozzi, G.J., Seigneuric, R., Neiers, F., Briand, L., Garrido, C.

Description: Structure of Nucleotide binding domain of HSP110, ATP and Mg2+ complexed
[[Category: Unreleased Structures]]
[[Category: Gotthard, G]]
[[Category: Gonzalez, D]]
[[Category: Neiers, F]]
[[Category: Briand, L]]
[[Category: Gozzi, G.J]]
[[Category: Seigneuric, R]]
[[Category: Garrido, C]]