5j27 - Revision history

OCA at 10:42, 6 September 2023

OCA — Wed, 06 Sep 2023 10:42:50 GMT

←Older revision		Revision as of 10:42, 6 September 2023
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	==HSP90 in complex with 5-[4-(2-Fluoro-phenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propyl-benzenesulfonamide==		==HSP90 in complex with 5-[4-(2-Fluoro-phenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propyl-benzenesulfonamide==
-	<StructureSection load='5j27' size='340' side='right' caption='[[5j27]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='5j27' size='340' side='right'caption='[[5j27]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j27]] 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=5J27 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5J27 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j27]] 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=5J27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J27 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6FF:5-[4-(2-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propylbenzene-1-sulfonamide'>6FF</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]] 1.7Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6FF:5-[4-(2-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propylbenzene-1-sulfonamide'>6FF</scene></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=5j27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j27 OCA], [~~http~~://pdbe.org/5j27 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5j27 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5j27 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5j27 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=5j27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j27 OCA], [https://pdbe.org/5j27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j27 RCSB], [https://www.ebi.ac.uk/pdbsum/5j27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j27 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 ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5j27" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5j27" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Heat Shock Protein structures\|Heat Shock Protein structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Amaral, M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Matias, P~~]]	+	[[Category: Amaral M]]
-	[[Category: ~~Chaperone]]~~	+	[[Category: Matias P]]
-	~~[[Category: Inhibitor~~]]	+

OCA at 20:36, 24 January 2018

OCA — Wed, 24 Jan 2018 20:36:05 GMT

←Older revision		Revision as of 20:36, 24 January 2018
Line 3:		Line 3:
	<StructureSection load='5j27' size='340' side='right' caption='[[5j27]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='5j27' size='340' side='right' caption='[[5j27]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j27]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J27 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j27]] 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=5J27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J27 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6FF:5-[4-(2-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propylbenzene-1-sulfonamide'>6FF</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6FF:5-[4-(2-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propylbenzene-1-sulfonamide'>6FF</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([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=5j27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j27 OCA], [http://pdbe.org/5j27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j27 RCSB], [http://www.ebi.ac.uk/pdbsum/5j27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j27 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=5j27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j27 OCA], [http://pdbe.org/5j27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j27 RCSB], [http://www.ebi.ac.uk/pdbsum/5j27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j27 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>		[[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;">
		+	== Publication Abstract from PubMed ==
		+	Structure-based drug design has often been restricted by the rather static picture of protein-ligand complexes presented by crystal structures, despite the widely accepted importance of protein flexibility in biomolecular recognition. Here we report a detailed experimental and computational study of the drug target, human heat shock protein 90, to explore the contribution of protein dynamics to the binding thermodynamics and kinetics of drug-like compounds. We observe that their binding properties depend on whether the protein has a loop or a helical conformation in the binding site of the ligand-bound state. Compounds bound to the helical conformation display slow association and dissociation rates, high-affinity and high cellular efficacy, and predominantly entropically driven binding. An important entropic contribution comes from the greater flexibility of the helical relative to the loop conformation in the ligand-bound state. This unusual mechanism suggests increasing target flexibility in the bound state by ligand design as a new strategy for drug discovery.
		+
		+	Protein conformational flexibility modulates kinetics and thermodynamics of drug binding.,Amaral M, Kokh DB, Bomke J, Wegener A, Buchstaller HP, Eggenweiler HM, Matias P, Sirrenberg C, Wade RC, Frech M Nat Commun. 2017 Dec 22;8(1):2276. doi: 10.1038/s41467-017-02258-w. PMID:29273709<ref>PMID:29273709</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5j27" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Amaral, M]]		[[Category: Amaral, M]]
	[[Category: Matias, P]]		[[Category: Matias, P]]
	[[Category: Chaperone]]		[[Category: Chaperone]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]

OCA at 07:07, 6 December 2017

OCA — Wed, 06 Dec 2017 07:07:21 GMT

←Older revision		Revision as of 07:07, 6 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5j27 is ON HOLD until Paper Publication~~	+	==HSP90 in complex with 5-[4-(2-Fluoro-phenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propyl-benzenesulfonamide==
-		+	<StructureSection load='5j27' size='340' side='right' caption='[[5j27]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~Authors: Amaral, M., Matias, P.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5j27]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J27 FirstGlance]. <br>
-	~~Description:~~ HSP90 in complex with 5-[4-(2-Fluoro-phenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propyl-benzenesulfonamide	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6FF:5-[4-(2-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propylbenzene-1-sulfonamide'>6FF</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=5j27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j27 OCA], [http://pdbe.org/5j27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j27 RCSB], [http://www.ebi.ac.uk/pdbsum/5j27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j27 ProSAT]</span></td></tr>
		+	</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Amaral, M]]
	[[Category: Matias, P]]		[[Category: Matias, P]]
-	[[Category: ~~Amaral, M~~]]	+	[[Category: Chaperone]]
		+	[[Category: Inhibitor]]

OCA at 07:50, 5 April 2017

OCA — Wed, 05 Apr 2017 07:50:15 GMT

←Older revision		Revision as of 07:50, 5 April 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5j27 is ON HOLD	+	The entry 5j27 is ON HOLD until Paper Publication

	Authors: Amaral, M., Matias, P.		Authors: Amaral, M., Matias, P.

OCA: Protected "5j27" [edit=sysop:move=sysop]

OCA — Wed, 11 May 2016 01:20:43 GMT

Protected "5j27" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:20, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5j27 is ON HOLD Authors: Amaral, M., Matias, P. Description: HSP90 in complex with 5-[4-(2-Fluoro-phenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]...

OCA — Wed, 11 May 2016 01:20:41 GMT

New page: '''Unreleased structure''' The entry 5j27 is ON HOLD Authors: Amaral, M., Matias, P. Description: HSP90 in complex with 5-[4-(2-Fluoro-phenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]...

New page

'''Unreleased structure'''

The entry 5j27 is ON HOLD

Authors: Amaral, M., Matias, P.

Description: HSP90 in complex with 5-[4-(2-Fluoro-phenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-2,4-dihydroxy-N-methyl-N-propyl-benzenesulfonamide
[[Category: Unreleased Structures]]
[[Category: Matias, P]]
[[Category: Amaral, M]]