2yi7 - Revision history

OCA at 07:12, 1 May 2024

2024-05-01T07:12:12Z

←Older revision		Revision as of 07:12, 1 May 2024
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	== Function ==		== Function ==
	[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>		[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>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	A potential therapeutic strategy for targeting cancer that has gained much interest is the inhibition of the ATP binding and ATPase activity of the molecular chaperone Hsp90. We have determined the structure of the human Hsp90alpha N-terminal domain in complex with a series of 5-aryl-4-(5-substituted-2-4-dihydroxyphenyl)-1,2,3-thiadiazoles. The structures provide the molecular details for the activity of these inhibitors. One of these inhibitors, ICPD 34, causes a structural change that affects a mobile loop, which adopts a conformation similar to that seen in complexes with ADP, rather than the conformation generally seen with the pyrazole/isoxazole-resorcinol class of inhibitors. Competitive binding to the Hsp90 N-terminal domain was observed in a biochemical assay, and these compounds showed antiproliferative activity and induced apoptosis in the HCT116 human colon cancer cell line. These inhibitors also caused induction of the heat shock response with the upregulation of Hsp72 and Hsp27 protein expression and the depletion of Hsp90 clients, CRAF, ERBB2 and CDK4, thus confirming that antiproliferative activity was through the inhibition of Hsp90. The presence of increased levels of the cleavage product of PARP indicated apoptosis in response to Hsp90 inhibitors. This work provides a framework for the further optimization of thiadiazole inhibitors of Hsp90. Importantly, we demonstrate that the thiadiazole inhibitors display a more limited core set of interactions relative to the clinical trial candidate NVP-AUY922, and consequently may be less susceptible to resistance derived through mutations in Hsp90.
-
-	Co-crystalization and in vitro biological characterization of 5-aryl-4-(5-substituted-2-4-dihydroxyphenyl)-1,2,3-thiadiazole hsp90 inhibitors.,Sharp SY, Roe SM, Kazlauskas E, Cikotiene I, Workman P, Matulis D, Prodromou C PLoS One. 2012;7(9):e44642. Epub 2012 Sep 11. PMID:22984537<ref>PMID:22984537</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 2yi7" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 14:04, 1 February 2024

2024-02-01T14:04:40Z

←Older revision		Revision as of 14:04, 1 February 2024
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	<StructureSection load='2yi7' size='340' side='right'caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='2yi7' size='340' side='right'caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2yi7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2yi7]] 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=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.4Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2yi0\|2yi0]], [[1osf\|1osf]], [[2bsm\|2bsm]], [[2wi3\|2wi3]], [[2ye4\|2ye4]], [[2ye5\|2ye5]], [[2bz5\|2bz5]], [[2ccs\|2ccs]], [[2yei\|2yei]], [[2yeg\|2yeg]], [[1uyi\|1uyi]], [[1yc3\|1yc3]], [[1uyf\|1uyf]], [[2ye3\|2ye3]], [[2byi\|2byi]], [[2vci\|2vci]], [[2wi1\|2wi1]], [[2xjx\|2xjx]], [[2fwz\|2fwz]], [[2xdk\|2xdk]], [[2xjg\|2xjg]], [[1uyh\|1uyh]], [[2fwy\|2fwy]], [[1uye\|1uye]], [[1uyl\|1uyl]], [[2xab\|2xab]], [[2yeh\|2yeh]], [[1uy7\|1uy7]], [[2xht\|2xht]], [[2xhr\|2xhr]], [[2yef\|2yef]], [[2byh\|2byh]], [[2wi5\|2wi5]], [[2cdd\|2cdd]], [[1uy9\|1uy9]], [[1yes\|1yes]], [[1byq\|1byq]], [[1uy8\|1uy8]], [[2wi4\|2wi4]], [[2bug\|2bug]], [[2uwd\|2uwd]], [[2yeb\|2yeb]], [[2ye7\|2ye7]], [[2xhx\|2xhx]], [[2wi7\|2wi7]], [[2yej\|2yej]], [[2bt0\|2bt0]], [[1yer\|1yer]], [[2xdu\|2xdu]], [[2yec\|2yec]], [[1uyg\|1uyg]], [[2ccu\|2ccu]], [[2xds\|2xds]], [[2xdx\|2xdx]], [[2xk2\|2xk2]], [[2xjj\|2xjj]], [[1uyd\|1uyd]], [[2xdl\|2xdl]], [[2wi2\|2wi2]], [[1uy6\|1uy6]], [[2yee\|2yee]], [[2ye2\|2ye2]], [[2vcj\|2vcj]], [[1yc4\|1yc4]], [[2ye9\|2ye9]], [[2c2l\|2c2l]], [[1uyk\|1uyk]], [[2cct\|2cct]], [[2wi6\|2wi6]], [[1yc1\|1yc1]], [[2yea\|2yea]], [[2ye6\|2ye6]], [[2yed\|2yed]], [[1uyc\|1uyc]], [[1yet\|1yet]], [[2jjc\|2jjc]], [[2ye8\|2ye8]], [[2yi6\|2yi6]], [[2yi5\|2yi5]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [https://pdbe.org/2yi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [https://www.ebi.ac.uk/pdbsum/2yi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yi7 ProSAT]</span></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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [https://pdbe.org/2yi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [https://www.ebi.ac.uk/pdbsum/2yi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yi7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[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>	+	[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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Pearl~~, L H~~]]	+	[[Category: Pearl LH]]
-	[[Category: Prodromou, C]]	+	[[Category: Prodromou C]]
-	[[Category: Roe~~, S M]]~~	+	[[Category: Roe SM]]
-	~~[[Category: Atpase]]~~	+
-	~~[[Category: Chaperone~~]]	+

OCA at 12:30, 27 April 2022

2022-04-27T12:30:32Z

←Older revision		Revision as of 12:30, 27 April 2022
Line 3:		Line 3:
	<StructureSection load='2yi7' size='340' side='right'caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='2yi7' size='340' side='right'caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2yi7]] 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=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2yi7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</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" id="ligandDat"><scene name='pdbligand=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2yi0\|2yi0]], [[1osf\|1osf]], [[2bsm\|2bsm]], [[2wi3\|2wi3]], [[2ye4\|2ye4]], [[2ye5\|2ye5]], [[2bz5\|2bz5]], [[2ccs\|2ccs]], [[2yei\|2yei]], [[2yeg\|2yeg]], [[1uyi\|1uyi]], [[1yc3\|1yc3]], [[1uyf\|1uyf]], [[2ye3\|2ye3]], [[2byi\|2byi]], [[2vci\|2vci]], [[2wi1\|2wi1]], [[2xjx\|2xjx]], [[2fwz\|2fwz]], [[2xdk\|2xdk]], [[2xjg\|2xjg]], [[1uyh\|1uyh]], [[2fwy\|2fwy]], [[1uye\|1uye]], [[1uyl\|1uyl]], [[2xab\|2xab]], [[2yeh\|2yeh]], [[1uy7\|1uy7]], [[2xht\|2xht]], [[2xhr\|2xhr]], [[2yef\|2yef]], [[2byh\|2byh]], [[2wi5\|2wi5]], [[2cdd\|2cdd]], [[1uy9\|1uy9]], [[1yes\|1yes]], [[1byq\|1byq]], [[1uy8\|1uy8]], [[2wi4\|2wi4]], [[2bug\|2bug]], [[2uwd\|2uwd]], [[2yeb\|2yeb]], [[2ye7\|2ye7]], [[2xhx\|2xhx]], [[2wi7\|2wi7]], [[2yej\|2yej]], [[2bt0\|2bt0]], [[1yer\|1yer]], [[2xdu\|2xdu]], [[2yec\|2yec]], [[1uyg\|1uyg]], [[2ccu\|2ccu]], [[2xds\|2xds]], [[2xdx\|2xdx]], [[2xk2\|2xk2]], [[2xjj\|2xjj]], [[1uyd\|1uyd]], [[2xdl\|2xdl]], [[2wi2\|2wi2]], [[1uy6\|1uy6]], [[2yee\|2yee]], [[2ye2\|2ye2]], [[2vcj\|2vcj]], [[1yc4\|1yc4]], [[2ye9\|2ye9]], [[2c2l\|2c2l]], [[1uyk\|1uyk]], [[2cct\|2cct]], [[2wi6\|2wi6]], [[1yc1\|1yc1]], [[2yea\|2yea]], [[2ye6\|2ye6]], [[2yed\|2yed]], [[1uyc\|1uyc]], [[1yet\|1yet]], [[2jjc\|2jjc]], [[2ye8\|2ye8]], [[2yi6\|2yi6]], [[2yi5\|2yi5]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2yi0\|2yi0]], [[1osf\|1osf]], [[2bsm\|2bsm]], [[2wi3\|2wi3]], [[2ye4\|2ye4]], [[2ye5\|2ye5]], [[2bz5\|2bz5]], [[2ccs\|2ccs]], [[2yei\|2yei]], [[2yeg\|2yeg]], [[1uyi\|1uyi]], [[1yc3\|1yc3]], [[1uyf\|1uyf]], [[2ye3\|2ye3]], [[2byi\|2byi]], [[2vci\|2vci]], [[2wi1\|2wi1]], [[2xjx\|2xjx]], [[2fwz\|2fwz]], [[2xdk\|2xdk]], [[2xjg\|2xjg]], [[1uyh\|1uyh]], [[2fwy\|2fwy]], [[1uye\|1uye]], [[1uyl\|1uyl]], [[2xab\|2xab]], [[2yeh\|2yeh]], [[1uy7\|1uy7]], [[2xht\|2xht]], [[2xhr\|2xhr]], [[2yef\|2yef]], [[2byh\|2byh]], [[2wi5\|2wi5]], [[2cdd\|2cdd]], [[1uy9\|1uy9]], [[1yes\|1yes]], [[1byq\|1byq]], [[1uy8\|1uy8]], [[2wi4\|2wi4]], [[2bug\|2bug]], [[2uwd\|2uwd]], [[2yeb\|2yeb]], [[2ye7\|2ye7]], [[2xhx\|2xhx]], [[2wi7\|2wi7]], [[2yej\|2yej]], [[2bt0\|2bt0]], [[1yer\|1yer]], [[2xdu\|2xdu]], [[2yec\|2yec]], [[1uyg\|1uyg]], [[2ccu\|2ccu]], [[2xds\|2xds]], [[2xdx\|2xdx]], [[2xk2\|2xk2]], [[2xjj\|2xjj]], [[1uyd\|1uyd]], [[2xdl\|2xdl]], [[2wi2\|2wi2]], [[1uy6\|1uy6]], [[2yee\|2yee]], [[2ye2\|2ye2]], [[2vcj\|2vcj]], [[1yc4\|1yc4]], [[2ye9\|2ye9]], [[2c2l\|2c2l]], [[1uyk\|1uyk]], [[2cct\|2cct]], [[2wi6\|2wi6]], [[1yc1\|1yc1]], [[2yea\|2yea]], [[2ye6\|2ye6]], [[2yed\|2yed]], [[1uyc\|1uyc]], [[1yet\|1yet]], [[2jjc\|2jjc]], [[2ye8\|2ye8]], [[2yi6\|2yi6]], [[2yi5\|2yi5]]</div></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [~~http~~://pdbe.org/2yi7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2yi7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2yi7 ProSAT]</span></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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [https://pdbe.org/2yi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [https://www.ebi.ac.uk/pdbsum/2yi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yi7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~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>	+	[[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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 12:52, 22 July 2020

2020-07-22T12:52:04Z

←Older revision		Revision as of 12:52, 22 July 2020
Line 1:		Line 1:

	==Structural characterization of 5-Aryl-4-(5-substituted-2-4- dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors.==		==Structural characterization of 5-Aryl-4-(5-substituted-2-4- dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors.==
-	<StructureSection load='2yi7' size='340' side='right' caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='2yi7' size='340' side='right'caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2yi7]] 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=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2yi7]] 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=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</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" id="ligandDat"><scene name='pdbligand=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2yi0\|2yi0]], [[1osf\|1osf]], [[2bsm\|2bsm]], [[2wi3\|2wi3]], [[2ye4\|2ye4]], [[2ye5\|2ye5]], [[2bz5\|2bz5]], [[2ccs\|2ccs]], [[2yei\|2yei]], [[2yeg\|2yeg]], [[1uyi\|1uyi]], [[1yc3\|1yc3]], [[1uyf\|1uyf]], [[2ye3\|2ye3]], [[2byi\|2byi]], [[2vci\|2vci]], [[2wi1\|2wi1]], [[2xjx\|2xjx]], [[2fwz\|2fwz]], [[2xdk\|2xdk]], [[2xjg\|2xjg]], [[1uyh\|1uyh]], [[2fwy\|2fwy]], [[1uye\|1uye]], [[1uyl\|1uyl]], [[2xab\|2xab]], [[2yeh\|2yeh]], [[1uy7\|1uy7]], [[2xht\|2xht]], [[2xhr\|2xhr]], [[2yef\|2yef]], [[2byh\|2byh]], [[2wi5\|2wi5]], [[2cdd\|2cdd]], [[1uy9\|1uy9]], [[1yes\|1yes]], [[1byq\|1byq]], [[1uy8\|1uy8]], [[2wi4\|2wi4]], [[2bug\|2bug]], [[2uwd\|2uwd]], [[2yeb\|2yeb]], [[2ye7\|2ye7]], [[2xhx\|2xhx]], [[2wi7\|2wi7]], [[2yej\|2yej]], [[2bt0\|2bt0]], [[1yer\|1yer]], [[2xdu\|2xdu]], [[2yec\|2yec]], [[1uyg\|1uyg]], [[2ccu\|2ccu]], [[2xds\|2xds]], [[2xdx\|2xdx]], [[2xk2\|2xk2]], [[2xjj\|2xjj]], [[1uyd\|1uyd]], [[2xdl\|2xdl]], [[2wi2\|2wi2]], [[1uy6\|1uy6]], [[2yee\|2yee]], [[2ye2\|2ye2]], [[2vcj\|2vcj]], [[1yc4\|1yc4]], [[2ye9\|2ye9]], [[2c2l\|2c2l]], [[1uyk\|1uyk]], [[2cct\|2cct]], [[2wi6\|2wi6]], [[1yc1\|1yc1]], [[2yea\|2yea]], [[2ye6\|2ye6]], [[2yed\|2yed]], [[1uyc\|1uyc]], [[1yet\|1yet]], [[2jjc\|2jjc]], [[2ye8\|2ye8]], [[2yi6\|2yi6]], [[2yi5\|2yi5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2yi0\|2yi0]], [[1osf\|1osf]], [[2bsm\|2bsm]], [[2wi3\|2wi3]], [[2ye4\|2ye4]], [[2ye5\|2ye5]], [[2bz5\|2bz5]], [[2ccs\|2ccs]], [[2yei\|2yei]], [[2yeg\|2yeg]], [[1uyi\|1uyi]], [[1yc3\|1yc3]], [[1uyf\|1uyf]], [[2ye3\|2ye3]], [[2byi\|2byi]], [[2vci\|2vci]], [[2wi1\|2wi1]], [[2xjx\|2xjx]], [[2fwz\|2fwz]], [[2xdk\|2xdk]], [[2xjg\|2xjg]], [[1uyh\|1uyh]], [[2fwy\|2fwy]], [[1uye\|1uye]], [[1uyl\|1uyl]], [[2xab\|2xab]], [[2yeh\|2yeh]], [[1uy7\|1uy7]], [[2xht\|2xht]], [[2xhr\|2xhr]], [[2yef\|2yef]], [[2byh\|2byh]], [[2wi5\|2wi5]], [[2cdd\|2cdd]], [[1uy9\|1uy9]], [[1yes\|1yes]], [[1byq\|1byq]], [[1uy8\|1uy8]], [[2wi4\|2wi4]], [[2bug\|2bug]], [[2uwd\|2uwd]], [[2yeb\|2yeb]], [[2ye7\|2ye7]], [[2xhx\|2xhx]], [[2wi7\|2wi7]], [[2yej\|2yej]], [[2bt0\|2bt0]], [[1yer\|1yer]], [[2xdu\|2xdu]], [[2yec\|2yec]], [[1uyg\|1uyg]], [[2ccu\|2ccu]], [[2xds\|2xds]], [[2xdx\|2xdx]], [[2xk2\|2xk2]], [[2xjj\|2xjj]], [[1uyd\|1uyd]], [[2xdl\|2xdl]], [[2wi2\|2wi2]], [[1uy6\|1uy6]], [[2yee\|2yee]], [[2ye2\|2ye2]], [[2vcj\|2vcj]], [[1yc4\|1yc4]], [[2ye9\|2ye9]], [[2c2l\|2c2l]], [[1uyk\|1uyk]], [[2cct\|2cct]], [[2wi6\|2wi6]], [[1yc1\|1yc1]], [[2yea\|2yea]], [[2ye6\|2ye6]], [[2yed\|2yed]], [[1uyc\|1uyc]], [[1yet\|1yet]], [[2jjc\|2jjc]], [[2ye8\|2ye8]], [[2yi6\|2yi6]], [[2yi5\|2yi5]]</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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [http://pdbe.org/2yi7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [http://www.ebi.ac.uk/pdbsum/2yi7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yi7 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [http://pdbe.org/2yi7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [http://www.ebi.ac.uk/pdbsum/2yi7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yi7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 21:		Line 21:

	==See Also==		==See Also==
-	*[[Heat Shock ~~Proteins~~\|Heat Shock ~~Proteins~~]]	+	*[[Heat Shock Protein structures\|Heat Shock Protein structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Pearl, L H]]		[[Category: Pearl, L H]]
	[[Category: Prodromou, C]]		[[Category: Prodromou, C]]

OCA at 22:03, 5 August 2016

2016-08-05T22:03:02Z

←Older revision		Revision as of 22:03, 5 August 2016
Line 1:		Line 1:
		+
	==Structural characterization of 5-Aryl-4-(5-substituted-2-4- dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors.==		==Structural characterization of 5-Aryl-4-(5-substituted-2-4- dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors.==
	<StructureSection load='2yi7' size='340' side='right' caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='2yi7' size='340' side='right' caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2yi7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2yi7]] 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=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</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=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2yi0\|2yi0]], [[1osf\|1osf]], [[2bsm\|2bsm]], [[2wi3\|2wi3]], [[2ye4\|2ye4]], [[2ye5\|2ye5]], [[2bz5\|2bz5]], [[2ccs\|2ccs]], [[2yei\|2yei]], [[2yeg\|2yeg]], [[1uyi\|1uyi]], [[1yc3\|1yc3]], [[1uyf\|1uyf]], [[2ye3\|2ye3]], [[2byi\|2byi]], [[2vci\|2vci]], [[2wi1\|2wi1]], [[2xjx\|2xjx]], [[2fwz\|2fwz]], [[2xdk\|2xdk]], [[2xjg\|2xjg]], [[1uyh\|1uyh]], [[2fwy\|2fwy]], [[1uye\|1uye]], [[1uyl\|1uyl]], [[2xab\|2xab]], [[2yeh\|2yeh]], [[1uy7\|1uy7]], [[2xht\|2xht]], [[2xhr\|2xhr]], [[2yef\|2yef]], [[2byh\|2byh]], [[2wi5\|2wi5]], [[2cdd\|2cdd]], [[1uy9\|1uy9]], [[1yes\|1yes]], [[1byq\|1byq]], [[1uy8\|1uy8]], [[2wi4\|2wi4]], [[2bug\|2bug]], [[2uwd\|2uwd]], [[2yeb\|2yeb]], [[2ye7\|2ye7]], [[2xhx\|2xhx]], [[2wi7\|2wi7]], [[2yej\|2yej]], [[2bt0\|2bt0]], [[1yer\|1yer]], [[2xdu\|2xdu]], [[2yec\|2yec]], [[1uyg\|1uyg]], [[2ccu\|2ccu]], [[2xds\|2xds]], [[2xdx\|2xdx]], [[2xk2\|2xk2]], [[2xjj\|2xjj]], [[1uyd\|1uyd]], [[2xdl\|2xdl]], [[2wi2\|2wi2]], [[1uy6\|1uy6]], [[2yee\|2yee]], [[2ye2\|2ye2]], [[2vcj\|2vcj]], [[1yc4\|1yc4]], [[2ye9\|2ye9]], [[2c2l\|2c2l]], [[1uyk\|1uyk]], [[2cct\|2cct]], [[2wi6\|2wi6]], [[1yc1\|1yc1]], [[2yea\|2yea]], [[2ye6\|2ye6]], [[2yed\|2yed]], [[1uyc\|1uyc]], [[1yet\|1yet]], [[2jjc\|2jjc]], [[2ye8\|2ye8]], [[2yi6\|2yi6]], [[2yi5\|2yi5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2yi0\|2yi0]], [[1osf\|1osf]], [[2bsm\|2bsm]], [[2wi3\|2wi3]], [[2ye4\|2ye4]], [[2ye5\|2ye5]], [[2bz5\|2bz5]], [[2ccs\|2ccs]], [[2yei\|2yei]], [[2yeg\|2yeg]], [[1uyi\|1uyi]], [[1yc3\|1yc3]], [[1uyf\|1uyf]], [[2ye3\|2ye3]], [[2byi\|2byi]], [[2vci\|2vci]], [[2wi1\|2wi1]], [[2xjx\|2xjx]], [[2fwz\|2fwz]], [[2xdk\|2xdk]], [[2xjg\|2xjg]], [[1uyh\|1uyh]], [[2fwy\|2fwy]], [[1uye\|1uye]], [[1uyl\|1uyl]], [[2xab\|2xab]], [[2yeh\|2yeh]], [[1uy7\|1uy7]], [[2xht\|2xht]], [[2xhr\|2xhr]], [[2yef\|2yef]], [[2byh\|2byh]], [[2wi5\|2wi5]], [[2cdd\|2cdd]], [[1uy9\|1uy9]], [[1yes\|1yes]], [[1byq\|1byq]], [[1uy8\|1uy8]], [[2wi4\|2wi4]], [[2bug\|2bug]], [[2uwd\|2uwd]], [[2yeb\|2yeb]], [[2ye7\|2ye7]], [[2xhx\|2xhx]], [[2wi7\|2wi7]], [[2yej\|2yej]], [[2bt0\|2bt0]], [[1yer\|1yer]], [[2xdu\|2xdu]], [[2yec\|2yec]], [[1uyg\|1uyg]], [[2ccu\|2ccu]], [[2xds\|2xds]], [[2xdx\|2xdx]], [[2xk2\|2xk2]], [[2xjj\|2xjj]], [[1uyd\|1uyd]], [[2xdl\|2xdl]], [[2wi2\|2wi2]], [[1uy6\|1uy6]], [[2yee\|2yee]], [[2ye2\|2ye2]], [[2vcj\|2vcj]], [[1yc4\|1yc4]], [[2ye9\|2ye9]], [[2c2l\|2c2l]], [[1uyk\|1uyk]], [[2cct\|2cct]], [[2wi6\|2wi6]], [[1yc1\|1yc1]], [[2yea\|2yea]], [[2ye6\|2ye6]], [[2yed\|2yed]], [[1uyc\|1uyc]], [[1yet\|1yet]], [[2jjc\|2jjc]], [[2ye8\|2ye8]], [[2yi6\|2yi6]], [[2yi5\|2yi5]]</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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [http://www.ebi.ac.uk/pdbsum/2yi7 PDBsum]</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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [http://pdbe.org/2yi7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [http://www.ebi.ac.uk/pdbsum/2yi7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yi7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2yi7" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Pearl, L H]]		[[Category: Pearl, L H]]
	[[Category: Prodromou, C]]		[[Category: Prodromou, C]]

OCA at 06:13, 25 December 2014

2014-12-25T06:13:15Z

←Older revision		Revision as of 06:13, 25 December 2014
Line 7:		Line 7:
	<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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [http://www.ebi.ac.uk/pdbsum/2yi7 PDBsum]</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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [http://www.ebi.ac.uk/pdbsum/2yi7 PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 15:		Line 17:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+
		+	==See Also==
		+	*[[Heat Shock Proteins\|Heat Shock Proteins]]
	== References ==		== References ==
	<references/>		<references/>
Line 20:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Pearl, L H.]]	+	[[Category: Pearl, L H]]
-	[[Category: Prodromou, C.]]	+	[[Category: Prodromou, C]]
-	[[Category: Roe, S M.]]	+	[[Category: Roe, S M]]
	[[Category: Atpase]]		[[Category: Atpase]]
	[[Category: Chaperone]]		[[Category: Chaperone]]

OCA at 12:01, 29 October 2014

2014-10-29T12:01:39Z

←Older revision		Revision as of 12:01, 29 October 2014
Line 1:		Line 1:
-	[[~~Image:~~2yi7.~~png~~\|~~left~~\|~~200px~~]]	+	==Structural characterization of 5-Aryl-4-(5-substituted-2-4- dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors.==
		+	<StructureSection load='2yi7' size='340' side='right' caption='[[2yi7]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2yi7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YI7 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BZ8:4-CHLORO-6-[5-(4-ETHOXYPHENYL)-1,2,3-THIADIAZOL-4-YL+BENZENE-1,3-DIOL'>BZ8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2yi0\|2yi0]], [[1osf\|1osf]], [[2bsm\|2bsm]], [[2wi3\|2wi3]], [[2ye4\|2ye4]], [[2ye5\|2ye5]], [[2bz5\|2bz5]], [[2ccs\|2ccs]], [[2yei\|2yei]], [[2yeg\|2yeg]], [[1uyi\|1uyi]], [[1yc3\|1yc3]], [[1uyf\|1uyf]], [[2ye3\|2ye3]], [[2byi\|2byi]], [[2vci\|2vci]], [[2wi1\|2wi1]], [[2xjx\|2xjx]], [[2fwz\|2fwz]], [[2xdk\|2xdk]], [[2xjg\|2xjg]], [[1uyh\|1uyh]], [[2fwy\|2fwy]], [[1uye\|1uye]], [[1uyl\|1uyl]], [[2xab\|2xab]], [[2yeh\|2yeh]], [[1uy7\|1uy7]], [[2xht\|2xht]], [[2xhr\|2xhr]], [[2yef\|2yef]], [[2byh\|2byh]], [[2wi5\|2wi5]], [[2cdd\|2cdd]], [[1uy9\|1uy9]], [[1yes\|1yes]], [[1byq\|1byq]], [[1uy8\|1uy8]], [[2wi4\|2wi4]], [[2bug\|2bug]], [[2uwd\|2uwd]], [[2yeb\|2yeb]], [[2ye7\|2ye7]], [[2xhx\|2xhx]], [[2wi7\|2wi7]], [[2yej\|2yej]], [[2bt0\|2bt0]], [[1yer\|1yer]], [[2xdu\|2xdu]], [[2yec\|2yec]], [[1uyg\|1uyg]], [[2ccu\|2ccu]], [[2xds\|2xds]], [[2xdx\|2xdx]], [[2xk2\|2xk2]], [[2xjj\|2xjj]], [[1uyd\|1uyd]], [[2xdl\|2xdl]], [[2wi2\|2wi2]], [[1uy6\|1uy6]], [[2yee\|2yee]], [[2ye2\|2ye2]], [[2vcj\|2vcj]], [[1yc4\|1yc4]], [[2ye9\|2ye9]], [[2c2l\|2c2l]], [[1uyk\|1uyk]], [[2cct\|2cct]], [[2wi6\|2wi6]], [[1yc1\|1yc1]], [[2yea\|2yea]], [[2ye6\|2ye6]], [[2yed\|2yed]], [[1uyc\|1uyc]], [[1yet\|1yet]], [[2jjc\|2jjc]], [[2ye8\|2ye8]], [[2yi6\|2yi6]], [[2yi5\|2yi5]]</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=2yi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yi7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yi7 RCSB], [http://www.ebi.ac.uk/pdbsum/2yi7 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A potential therapeutic strategy for targeting cancer that has gained much interest is the inhibition of the ATP binding and ATPase activity of the molecular chaperone Hsp90. We have determined the structure of the human Hsp90alpha N-terminal domain in complex with a series of 5-aryl-4-(5-substituted-2-4-dihydroxyphenyl)-1,2,3-thiadiazoles. The structures provide the molecular details for the activity of these inhibitors. One of these inhibitors, ICPD 34, causes a structural change that affects a mobile loop, which adopts a conformation similar to that seen in complexes with ADP, rather than the conformation generally seen with the pyrazole/isoxazole-resorcinol class of inhibitors. Competitive binding to the Hsp90 N-terminal domain was observed in a biochemical assay, and these compounds showed antiproliferative activity and induced apoptosis in the HCT116 human colon cancer cell line. These inhibitors also caused induction of the heat shock response with the upregulation of Hsp72 and Hsp27 protein expression and the depletion of Hsp90 clients, CRAF, ERBB2 and CDK4, thus confirming that antiproliferative activity was through the inhibition of Hsp90. The presence of increased levels of the cleavage product of PARP indicated apoptosis in response to Hsp90 inhibitors. This work provides a framework for the further optimization of thiadiazole inhibitors of Hsp90. Importantly, we demonstrate that the thiadiazole inhibitors display a more limited core set of interactions relative to the clinical trial candidate NVP-AUY922, and consequently may be less susceptible to resistance derived through mutations in Hsp90.

-	~~{{STRUCTURE_2yi7\| PDB=2yi7 \| SCENE= }}~~	+	Co-crystalization and in vitro biological characterization of 5-aryl-4-(5-substituted-2-4-dihydroxyphenyl)-1,2,3-thiadiazole hsp90 inhibitors.,Sharp SY, Roe SM, Kazlauskas E, Cikotiene I, Workman P, Matulis D, Prodromou C PLoS One. 2012;7(9):e44642. Epub 2012 Sep 11. PMID:22984537<ref>PMID:22984537</ref>

-	~~===Structural characterization~~ of ~~5-Aryl-4-(5-substituted-2-4- dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors~~.~~===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_22984537}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[2yi7]] is a 1 chain structure with sequence from [http:~~/~~/en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA].~~	+	</StructureSection>
-		+
-	~~==See Also==~~	+
-	*[[Heat Shock Proteins\|Heat Shock Proteins]]	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Pearl, L H.]]		[[Category: Pearl, L H.]]

OCA at 13:33, 20 October 2012

2012-10-20T13:33:30Z

←Older revision		Revision as of 13:33, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2yi7]] is a 1 chain structure ~~of [[Heat Shock Proteins]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA].	+	[[2yi7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA].

	==See Also==		==See Also==

OCA at 20:34, 26 September 2012

2012-09-26T20:34:32Z

←Older revision		Revision as of 20:34, 26 September 2012
Line 5:		Line 5:
	===Structural characterization of 5-Aryl-4-(5-substituted-2-4- dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors.===		===Structural characterization of 5-Aryl-4-(5-substituted-2-4- dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors.===

		+	{{ABSTRACT_PUBMED_22984537}}

	==About this Structure==		==About this Structure==

OCA at 12:21, 26 July 2012

2012-07-26T12:21:28Z

←Older revision		Revision as of 12:21, 26 July 2012
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-	[[Image:2yi7.~~jpg~~\|left\|200px]]	+	[[Image:2yi7.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_2yi7\| PDB=2yi7 \| SCENE= }}		{{STRUCTURE_2yi7\| PDB=2yi7 \| SCENE= }}

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	==About this Structure==		==About this Structure==
-	[[2yi7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA].	+	[[2yi7]] is a 1 chain structure of [[Heat Shock Proteins]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YI7 OCA].
		+
		+	==See Also==
		+	*[[Heat Shock Proteins\|Heat Shock Proteins]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Pearl, L H.]]		[[Category: Pearl, L H.]]