3hhu - Revision history

OCA at 09:59, 21 February 2024

OCA — Wed, 21 Feb 2024 09:59:59 GMT

←Older revision		Revision as of 09:59, 21 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HHU FirstGlance]. <br>		<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HHU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</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]] 1.59Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1byq\|1byq]], [[1osf\|1osf]], [[1uy6\|1uy6]], [[1yc1\|1yc1]], [[1yet\|1yet]], [[2bsm\|2bsm]], [[2bto\|2bto]], [[2byi\|2byi]], [[2c2l\|2c2l]], [[2cct\|2cct]], [[2ccu\|2ccu]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</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=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [https://pdbe.org/3hhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [https://www.ebi.ac.uk/pdbsum/3hhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hhu 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=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [https://pdbe.org/3hhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [https://www.ebi.ac.uk/pdbsum/3hhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hhu 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 20:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hhu ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hhu ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Heat-shock protein-90 is an attractive target for anticancer drugs, as heat-shock protein-90 blockers such as the ansamycin 17-(allylamino)-17-demethoxygeldanamycin greatly reduce the expression of many signaling molecules that are disregulated in cancer cells and are key drivers of tumor growth and metastasis. While 17-(allylamino)-17-demethoxygeldanamycin has shown promise in clinical trials, this compound class has significant template-related drawbacks. In this paper, we describe a new, potent non-ansamycin small-molecule inhibitor of heat-shock protein-90, BX-2819, containing resorcinol and triazolothione rings. Structural studies demonstrate binding of BX-2819 to the ADP/ATP-binding pocket of heat-shock protein-90. The compound blocked expression of heat-shock protein-90 client proteins in cancer cell lines and inhibited cell growth with a potency similar to 17-(allylamino)-17-demethoxygeldanamycin. In a panel of four cancer cell lines, BX-2819 blocked growth with an average IC(50) value of 32 nM (range of 7-72 nM). Efficacy studies demonstrated that treatment with BX-2819 significantly inhibited the growth of NCI-N87 and HT-29 tumors in nude mice, consistent with pharmacodynamic studies showing inhibition of heat-shock protein-90 client protein expression in tumors for greater than 16 h after dosing. These data support further studies to assess the potential of BX-2819 and related analogs for the treatment of cancer.
-
-	Potent triazolothione inhibitor of heat-shock protein-90.,Feldman RI, Mintzer B, Zhu D, Wu JM, Biroc SL, Yuan S, Emayan K, Chang Z, Chen D, Arnaiz DO, Bryant J, Ge XS, Whitlow M, Adler M, Polokoff MA, Li WW, Ferrer M, Sato T, Gu JM, Shen J, Tseng JL, Dinter H, Buckman B Chem Biol Drug Des. 2009 Jul;74(1):43-50. PMID:19519743<ref>PMID:19519743</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3hhu" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 29:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Adler, M]]	+	[[Category: Adler M]]
-	[[Category: Whitlow, M]]	+	[[Category: Whitlow M]]
-	~~[[Category: Alternative splicing]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Atpase]]~~	+
-	~~[[Category: Chaperone]]~~	+
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Heat shock]]~~	+
-	~~[[Category: Hsp90]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Stress response~~]]	+

OCA at 12:48, 23 March 2022

OCA — Wed, 23 Mar 2022 12:48:14 GMT

←Older revision		Revision as of 12:48, 23 March 2022
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	<StructureSection load='3hhu' size='340' side='right'caption='[[3hhu]], [[Resolution\|resolution]] 1.59Å' scene=''>		<StructureSection load='3hhu' size='340' side='right'caption='[[3hhu]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3HHU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HHU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1byq\|1byq]], [[1osf\|1osf]], [[1uy6\|1uy6]], [[1yc1\|1yc1]], [[1yet\|1yet]], [[2bsm\|2bsm]], [[2bto\|2bto]], [[2byi\|2byi]], [[2c2l\|2c2l]], [[2cct\|2cct]], [[2ccu\|2ccu]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1byq\|1byq]], [[1osf\|1osf]], [[1uy6\|1uy6]], [[1yc1\|1yc1]], [[1yet\|1yet]], [[2bsm\|2bsm]], [[2bto\|2bto]], [[2byi\|2byi]], [[2c2l\|2c2l]], [[2cct\|2cct]], [[2ccu\|2ccu]]</div></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=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [~~http~~://pdbe.org/3hhu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3hhu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3hhu 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=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [https://pdbe.org/3hhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [https://www.ebi.ac.uk/pdbsum/3hhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hhu 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 06:39, 7 August 2019

OCA — Wed, 07 Aug 2019 06:39:24 GMT

←Older revision		Revision as of 06:39, 7 August 2019
Line 1:		Line 1:

	==Human heat-shock protein 90 (HSP90) in complex with {4-[3-(2,4-dihydroxy-5-isopropyl-phenyl)-5-thioxo- 1,5-dihydro-[1,2,4]triazol-4-yl]-benzyl}-carbamic acid ethyl ester {ZK 2819}==		==Human heat-shock protein 90 (HSP90) in complex with {4-[3-(2,4-dihydroxy-5-isopropyl-phenyl)-5-thioxo- 1,5-dihydro-[1,2,4]triazol-4-yl]-benzyl}-carbamic acid ethyl ester {ZK 2819}==
-	<StructureSection load='3hhu' size='340' side='right' caption='[[3hhu]], [[Resolution\|resolution]] 1.59Å' scene=''>	+	<StructureSection load='3hhu' size='340' side='right'caption='[[3hhu]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HHU FirstGlance]. <br>		<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HHU FirstGlance]. <br>
Line 14:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hh/3hhu_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hh/3hhu_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 29:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 3hhu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3hhu" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Heat Shock Protein structures\|Heat Shock Protein structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 34:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Adler, M]]		[[Category: Adler, M]]
	[[Category: Whitlow, M]]		[[Category: Whitlow, M]]

OCA at 07:36, 1 November 2017

OCA — Wed, 01 Nov 2017 07:36:36 GMT

←Older revision		Revision as of 07:36, 1 November 2017
Line 29:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 3hhu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3hhu" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Heat Shock Proteins\|Heat Shock Proteins]]
	== References ==		== References ==
	<references/>		<references/>
Line 37:		Line 34:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Adler,M]]	+	[[Category: Adler, M]]
-	[[Category: Whitlow,M]]	+	[[Category: Whitlow, M]]
		+	[[Category: Alternative splicing]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Atpase]]		[[Category: Atpase]]
	[[Category: Chaperone]]		[[Category: Chaperone]]
		+	[[Category: Cytoplasm]]
	[[Category: Heat shock]]		[[Category: Heat shock]]
	[[Category: Hsp90]]		[[Category: Hsp90]]

OCA at 18:21, 5 August 2016

OCA — Fri, 05 Aug 2016 18:21:40 GMT

←Older revision		Revision as of 18:21, 5 August 2016
Line 1:		Line 1:
		+
	==Human heat-shock protein 90 (HSP90) in complex with {4-[3-(2,4-dihydroxy-5-isopropyl-phenyl)-5-thioxo- 1,5-dihydro-[1,2,4]triazol-4-yl]-benzyl}-carbamic acid ethyl ester {ZK 2819}==		==Human heat-shock protein 90 (HSP90) in complex with {4-[3-(2,4-dihydroxy-5-isopropyl-phenyl)-5-thioxo- 1,5-dihydro-[1,2,4]triazol-4-yl]-benzyl}-carbamic acid ethyl ester {ZK 2819}==
	<StructureSection load='3hhu' size='340' side='right' caption='[[3hhu]], [[Resolution\|resolution]] 1.59Å' scene=''>		<StructureSection load='3hhu' size='340' side='right' caption='[[3hhu]], [[Resolution\|resolution]] 1.59Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1byq\|1byq]], [[1osf\|1osf]], [[1uy6\|1uy6]], [[1yc1\|1yc1]], [[1yet\|1yet]], [[2bsm\|2bsm]], [[2bto\|2bto]], [[2byi\|2byi]], [[2c2l\|2c2l]], [[2cct\|2cct]], [[2ccu\|2ccu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1byq\|1byq]], [[1osf\|1osf]], [[1uy6\|1uy6]], [[1yc1\|1yc1]], [[1yet\|1yet]], [[2bsm\|2bsm]], [[2bto\|2bto]], [[2byi\|2byi]], [[2c2l\|2c2l]], [[2cct\|2cct]], [[2ccu\|2ccu]]</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=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [http://www.ebi.ac.uk/pdbsum/3hhu 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=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [http://pdbe.org/3hhu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [http://www.ebi.ac.uk/pdbsum/3hhu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hhu ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hhu ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 27:		Line 28:
	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 3hhu" style="background-color:#fffaf0;"></div>

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

OCA at 20:56, 25 December 2014

OCA — Thu, 25 Dec 2014 20:56:04 GMT

←Older revision		Revision as of 20:56, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HHU FirstGlance]. <br>		<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HHU FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1byq\|1byq]], [[1osf\|1osf]], [[1uy6\|1uy6]], [[1yc1\|1yc1]], [[1yet\|1yet]], [[2bsm\|2bsm]], [[2bto\|2bto]], [[2byi\|2byi]], [[2c2l\|2c2l]], [[2cct\|2cct]], [[2ccu\|2ccu]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1byq\|1byq]], [[1osf\|1osf]], [[1uy6\|1uy6]], [[1yc1\|1yc1]], [[1yet\|1yet]], [[2bsm\|2bsm]], [[2bto\|2bto]], [[2byi\|2byi]], [[2c2l\|2c2l]], [[2cct\|2cct]], [[2ccu\|2ccu]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [http://www.ebi.ac.uk/pdbsum/3hhu 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=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [http://www.ebi.ac.uk/pdbsum/3hhu 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Adler,M.]]	+	[[Category: Adler,M]]
-	[[Category: Whitlow,M.]]	+	[[Category: Whitlow,M]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Atpase]]		[[Category: Atpase]]

OCA at 10:53, 29 September 2014

OCA — Mon, 29 Sep 2014 10:53:01 GMT

←Older revision		Revision as of 10:53, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~3hhu.~~png~~\|~~left~~\|200px]]	+	==Human heat-shock protein 90 (HSP90) in complex with {4-[3-(2,4-dihydroxy-5-isopropyl-phenyl)-5-thioxo- 1,5-dihydro-[1,2,4]triazol-4-yl]-benzyl}-carbamic acid ethyl ester {ZK 2819}==
		+	<StructureSection load='3hhu' size='340' side='right' caption='[[3hhu]], [[Resolution\|resolution]] 1.59Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3hhu]] is a 2 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=3HHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HHU FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=819:ETHYL+(4-{3-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL}BENZYL)CARBAMATE'>819</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1byq\|1byq]], [[1osf\|1osf]], [[1uy6\|1uy6]], [[1yc1\|1yc1]], [[1yet\|1yet]], [[2bsm\|2bsm]], [[2bto\|2bto]], [[2byi\|2byi]], [[2c2l\|2c2l]], [[2cct\|2cct]], [[2ccu\|2ccu]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hhu RCSB], [http://www.ebi.ac.uk/pdbsum/3hhu PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hh/3hhu_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Heat-shock protein-90 is an attractive target for anticancer drugs, as heat-shock protein-90 blockers such as the ansamycin 17-(allylamino)-17-demethoxygeldanamycin greatly reduce the expression of many signaling molecules that are disregulated in cancer cells and are key drivers of tumor growth and metastasis. While 17-(allylamino)-17-demethoxygeldanamycin has shown promise in clinical trials, this compound class has significant template-related drawbacks. In this paper, we describe a new, potent non-ansamycin small-molecule inhibitor of heat-shock protein-90, BX-2819, containing resorcinol and triazolothione rings. Structural studies demonstrate binding of BX-2819 to the ADP/ATP-binding pocket of heat-shock protein-90. The compound blocked expression of heat-shock protein-90 client proteins in cancer cell lines and inhibited cell growth with a potency similar to 17-(allylamino)-17-demethoxygeldanamycin. In a panel of four cancer cell lines, BX-2819 blocked growth with an average IC(50) value of 32 nM (range of 7-72 nM). Efficacy studies demonstrated that treatment with BX-2819 significantly inhibited the growth of NCI-N87 and HT-29 tumors in nude mice, consistent with pharmacodynamic studies showing inhibition of heat-shock protein-90 client protein expression in tumors for greater than 16 h after dosing. These data support further studies to assess the potential of BX-2819 and related analogs for the treatment of cancer.

-	~~{{STRUCTURE_3hhu\| PDB=3hhu \| SCENE= }}~~	+	Potent triazolothione inhibitor of heat-shock protein-90.,Feldman RI, Mintzer B, Zhu D, Wu JM, Biroc SL, Yuan S, Emayan K, Chang Z, Chen D, Arnaiz DO, Bryant J, Ge XS, Whitlow M, Adler M, Polokoff MA, Li WW, Ferrer M, Sato T, Gu JM, Shen J, Tseng JL, Dinter H, Buckman B Chem Biol Drug Des. 2009 Jul;74(1):43-50. PMID:19519743<ref>PMID:19519743</ref>

-	~~===Human heat-shock protein 90 (HSP90) in complex with {4-[3-(2~~,~~4-dihydroxy-5-isopropyl-phenyl)-5-thioxo- 1,5-dihydro-[1,2,4]triazol-4-yl]-benzyl}-carbamic acid ethyl ester {ZK 2819}===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_19519743}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3hhu]] is~~ a ~~2 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=3HHU OCA].~~	+

	==See Also==		==See Also==
	*[[Heat Shock Proteins\|Heat Shock Proteins]]		*[[Heat Shock Proteins\|Heat Shock Proteins]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:019519743<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Adler,M.]]		[[Category: Adler,M.]]

OCA at 21:32, 20 October 2012

OCA — Sat, 20 Oct 2012 21:32:02 GMT

←Older revision		Revision as of 21:32, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3hhu]] is a 2 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=3HHU OCA].	+	[[3hhu]] is a 2 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=3HHU OCA].

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

OCA at 13:32, 27 July 2012

OCA — Fri, 27 Jul 2012 13:32:51 GMT

←Older revision		Revision as of 13:32, 27 July 2012
Line 1:		Line 1:
	[[Image:3hhu.png\|left\|200px]]		[[Image:3hhu.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3hhu", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3hhu\| PDB=3hhu \| SCENE= }}		{{STRUCTURE_3hhu\| PDB=3hhu \| SCENE= }}

	===Human heat-shock protein 90 (HSP90) in complex with {4-[3-(2,4-dihydroxy-5-isopropyl-phenyl)-5-thioxo- 1,5-dihydro-[1,2,4]triazol-4-yl]-benzyl}-carbamic acid ethyl ester {ZK 2819}===		===Human heat-shock protein 90 (HSP90) in complex with {4-[3-(2,4-dihydroxy-5-isopropyl-phenyl)-5-thioxo- 1,5-dihydro-[1,2,4]triazol-4-yl]-benzyl}-carbamic acid ethyl ester {ZK 2819}===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19519743}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19519743 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19519743}}		{{ABSTRACT_PUBMED_19519743}}

Line 22:		Line 11:

	==See Also==		==See Also==
-	*[[Heat Shock Proteins]]	+	*[[Heat Shock Proteins\|Heat Shock Proteins]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19519743~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019519743</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Adler,M.]]		[[Category: Adler,M.]]
	[[Category: Whitlow,M.]]		[[Category: Whitlow,M.]]
-	[[Category: Alternative splicing]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Atpase]]		[[Category: Atpase]]
	[[Category: Chaperone]]		[[Category: Chaperone]]
-	[[Category: Cytoplasm]]
	[[Category: Heat shock]]		[[Category: Heat shock]]
	[[Category: Hsp90]]		[[Category: Hsp90]]

OCA: Protected "3hhu" [edit=sysop:move=sysop]

OCA — Sun, 26 Dec 2010 23:39:51 GMT

Protected "3hhu" [edit=sysop:move=sysop]

←Older revision

Revision as of 23:39, 26 December 2010