5lnz - Revision history

OCA at 18:37, 18 October 2023

2023-10-18T18:37:07Z

←Older revision		Revision as of 18:37, 18 October 2023
Line 1:		Line 1:

	==HSP90 WITH indazole derivative==		==HSP90 WITH indazole derivative==
-	<StructureSection load='5lnz' size='340' side='right' caption='[[5lnz]], [[Resolution\|resolution]] 1.54Å' scene=''>	+	<StructureSection load='5lnz' size='340' side='right'caption='[[5lnz]], [[Resolution\|resolution]] 1.54Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5lnz]] 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=5LNZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5LNZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5lnz]] 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=5LNZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LNZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70Z:~{N}3-butyl-~{N}3,~{N}5-dimethyl-~{N}5-(4-morpholin-4-ylphenyl)-6-oxidanyl-2~{H}-indazole-3,5-dicarboxamide'>70Z</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]] 1.54Å</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=70Z:~{N}3-butyl-~{N}3,~{N}5-dimethyl-~{N}5-(4-morpholin-4-ylphenyl)-6-oxidanyl-2~{H}-indazole-3,5-dicarboxamide'>70Z</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=5lnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lnz OCA], [~~http~~://pdbe.org/5lnz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5lnz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5lnz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5lnz 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=5lnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lnz OCA], [https://pdbe.org/5lnz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lnz RCSB], [https://www.ebi.ac.uk/pdbsum/5lnz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lnz 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 5lnz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5lnz" 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: ~~Graedler, U~~]]	+	[[Category: Amaral M]]
-	[[Category: ~~Schuetz, D~~]]	+	[[Category: Graedler U]]
-	[[Category: ~~Chaperone~~]]	+	[[Category: Schuetz D]]

OCA at 07:36, 23 May 2018

2018-05-23T07:36:26Z

←Older revision		Revision as of 07:36, 23 May 2018
Line 3:		Line 3:
	<StructureSection load='5lnz' size='340' side='right' caption='[[5lnz]], [[Resolution\|resolution]] 1.54Å' scene=''>		<StructureSection load='5lnz' size='340' side='right' caption='[[5lnz]], [[Resolution\|resolution]] 1.54Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5lnz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LNZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LNZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5lnz]] 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=5LNZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LNZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70Z:~{N}3-butyl-~{N}3,~{N}5-dimethyl-~{N}5-(4-morpholin-4-ylphenyl)-6-oxidanyl-2~{H}-indazole-3,5-dicarboxamide'>70Z</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70Z:~{N}3-butyl-~{N}3,~{N}5-dimethyl-~{N}5-(4-morpholin-4-ylphenyl)-6-oxidanyl-2~{H}-indazole-3,5-dicarboxamide'>70Z</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=5lnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lnz OCA], [http://pdbe.org/5lnz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lnz RCSB], [http://www.ebi.ac.uk/pdbsum/5lnz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lnz 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=5lnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lnz OCA], [http://pdbe.org/5lnz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lnz RCSB], [http://www.ebi.ac.uk/pdbsum/5lnz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lnz 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 ==
		+	Residence time and more recently the association rate constant kon are increasingly acknowledged as important parameters for in vivo efficacy and safety of drugs. However, their broader consideration in drug development is limited by a lack of knowledge of how to optimize these parameters. In this study on a set of 176 heat shock protein 90 inhibitors, structure-kinetic relationships, X-ray crystallography, and molecular dynamics simulations were combined to retrieve a concrete scheme of how to rationally slow down on-rates. We discovered that an increased ligand desolvation barrier by introducing polar substituents resulted in a significant kon decrease. The slowdown was accomplished by introducing polar moieties to those parts of the ligand that point toward a hydrophobic cavity. We validated this scheme by increasing polarity of three Hsp90 inhibitors and observed a 9-, 13-, and 45-fold slowdown of on-rates and a 9-fold prolongation in residence time. This prolongation was driven by transition state destabilization rather than ground state stabilization.
		+
		+	Ligand Desolvation Steers On-Rate and Impacts Drug Residence Time of Heat Shock Protein 90 (Hsp90) Inhibitors.,Schuetz DA, Richter L, Amaral M, Grandits M, Gradler U, Musil D, Buchstaller HP, Eggenweiler HM, Frech M, Ecker GF J Med Chem. 2018 May 10. doi: 10.1021/acs.jmedchem.8b00080. PMID:29701469<ref>PMID:29701469</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5lnz" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Amaral, M]]		[[Category: Amaral, M]]
	[[Category: Graedler, U]]		[[Category: Graedler, U]]
	[[Category: Schuetz, D]]		[[Category: Schuetz, D]]
	[[Category: Chaperone]]		[[Category: Chaperone]]

OCA at 06:05, 29 November 2017

2017-11-29T06:05:56Z

←Older revision		Revision as of 06:05, 29 November 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5lnz is ~~ON HOLD until Paper Publication~~	+	==HSP90 WITH indazole derivative==
-		+	<StructureSection load='5lnz' size='340' side='right' caption='[[5lnz]], [[Resolution\|resolution]] 1.54Å' scene=''>
-	~~Authors~~: ~~Graedler~~, U., ~~Amaral~~, M., ~~Schuetz~~, D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5lnz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LNZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LNZ FirstGlance]. <br>
-	~~Description~~: ~~HSP90 WITH indazole derivative~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70Z:~{N}3-butyl-~{N}3,~{N}5-dimethyl-~{N}5-(4-morpholin-4-ylphenyl)-6-oxidanyl-2~{H}-indazole-3,5-dicarboxamide'>70Z</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=5lnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lnz OCA], [http://pdbe.org/5lnz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lnz RCSB], [http://www.ebi.ac.uk/pdbsum/5lnz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lnz 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: Graedler, U]]
	[[Category: Schuetz, D]]		[[Category: Schuetz, D]]
-	[[Category: ~~Graedler, U]]~~	+	[[Category: Chaperone]]
-	~~[[Category: Amaral, M~~]]	+

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

2016-09-09T15:05:00Z

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

←Older revision

Revision as of 15:05, 9 September 2016

OCA: New page: '''Unreleased structure''' The entry 5lnz is ON HOLD until Paper Publication Authors: Graedler, U., Amaral, M., Schuetz, D. Description: HSP90 WITH indazole derivative [[Category: Unre...

2016-09-09T15:04:59Z

New page: '''Unreleased structure''' The entry 5lnz is ON HOLD until Paper Publication Authors: Graedler, U., Amaral, M., Schuetz, D. Description: HSP90 WITH indazole derivative [[Category: Unre...

New page

'''Unreleased structure'''

The entry 5lnz is ON HOLD until Paper Publication

Authors: Graedler, U., Amaral, M., Schuetz, D.

Description: HSP90 WITH indazole derivative
[[Category: Unreleased Structures]]
[[Category: Schuetz, D]]
[[Category: Graedler, U]]
[[Category: Amaral, M]]