5od7 - Revision history

OCA at 09:40, 6 December 2023

OCA — Wed, 06 Dec 2023 09:40:38 GMT

←Older revision		Revision as of 09:40, 6 December 2023
Line 3:		Line 3:
	<StructureSection load='5od7' size='340' side='right'caption='[[5od7]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5od7' size='340' side='right'caption='[[5od7]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5od7]] 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=5OD7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5OD7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5od7]] 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=5OD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OD7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H0T:[2-azanyl-6-[2-(4-methylpiperazin-1-yl)sulfonylphenyl]quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone'>H0T</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]] 2Å</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=H0T:[2-azanyl-6-[2-(4-methylpiperazin-1-yl)sulfonylphenyl]quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone'>H0T</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=5od7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5od7 OCA], [~~http~~://pdbe.org/5od7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5od7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5od7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5od7 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=5od7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5od7 OCA], [https://pdbe.org/5od7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5od7 RCSB], [https://www.ebi.ac.uk/pdbsum/5od7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5od7 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 ==
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	</div>		</div>
	<div class="pdbe-citations 5od7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5od7" 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: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Amaral, M]]	+	[[Category: Amaral M]]
-	[[Category: Buchstaller, H P]]	+	[[Category: Buchstaller H-P]]
-	[[Category: Ecker~~, G F~~]]	+	[[Category: Ecker GF]]
-	[[Category: Eggenweiler, H M]]	+	[[Category: Eggenweiler H-M]]
-	[[Category: Frech, M]]	+	[[Category: Frech M]]
-	[[Category: Graedler, U]]	+	[[Category: Graedler U]]
-	[[Category: Grandits, M]]	+	[[Category: Grandits M]]
-	[[Category: Lehmann, M]]	+	[[Category: Lehmann M]]
-	[[Category: Musil, D]]	+	[[Category: Musil D]]
-	[[Category: Richter, L]]	+	[[Category: Richter L]]
-	[[Category: Schuetz~~, D A]]~~	+	[[Category: Schuetz DA]]
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Atpase]]~~	+
-	~~[[Category: Chaperone]]~~	+
-	~~[[Category: Heat shock]]~~	+
-	~~[[Category: Heat-shock protein complex]]~~	+
-	~~[[Category: Hsp90]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Pyrazole~~]]	+

OCA at 22:57, 5 June 2019

OCA — Wed, 05 Jun 2019 22:57:39 GMT

←Older revision		Revision as of 22:57, 5 June 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5od7 is ~~ON HOLD~~	+	==Hsp90 inhibitor desolvation as a rationale to steer on-rates and impact residence time==
		+	<StructureSection load='5od7' size='340' side='right'caption='[[5od7]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5od7]] 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=5OD7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OD7 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H0T:[2-azanyl-6-[2-(4-methylpiperazin-1-yl)sulfonylphenyl]quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone'>H0T</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=5od7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5od7 OCA], [http://pdbe.org/5od7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5od7 RCSB], [http://www.ebi.ac.uk/pdbsum/5od7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5od7 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>
		+	<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.

-	~~Authors:~~ Schuetz~~, D.A.~~, Richter, L., Amaral, M., Grandits, M., ~~Musil~~, D~~., Graedler, U.~~, Buchstaller~~, H.-P.~~, Eggenweiler~~, H.-M.~~, Frech, M., Ecker~~, G~~.F.~~, Lehmann, M~~.	+	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>

-	~~Description: Hsp90 inhibitor desolvation as~~ a ~~rationale to steer on-rates and impact residence time~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Lehmann, M]]~~	+	<div class="pdbe-citations 5od7" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Graedler, U~~]]	+	== References ==
-	[[Category: ~~Frech, M~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Amaral, M]]		[[Category: Amaral, M]]
-	[[Category: Buchstaller, H.-P]]	+	[[Category: Buchstaller, H P]]
		+	[[Category: Ecker, G F]]
		+	[[Category: Eggenweiler, H M]]
		+	[[Category: Frech, M]]
		+	[[Category: Graedler, U]]
	[[Category: Grandits, M]]		[[Category: Grandits, M]]
-	[[Category: ~~Eggenweiler~~, ~~H.-~~M]]	+	[[Category: Lehmann, M]]
-	~~[[Category: Ecker, G.F]]~~	+
-	~~[[Category: Schuetz, D.A]]~~	+
-	~~[[Category: Richter, L~~]]	+
	[[Category: Musil, D]]		[[Category: Musil, D]]
		+	[[Category: Richter, L]]
		+	[[Category: Schuetz, D A]]
		+	[[Category: Atp-binding]]
		+	[[Category: Atpase]]
		+	[[Category: Chaperone]]
		+	[[Category: Heat shock]]
		+	[[Category: Heat-shock protein complex]]
		+	[[Category: Hsp90]]
		+	[[Category: Nucleotide-binding]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Pyrazole]]

OCA at 10:30, 7 November 2018

OCA — Wed, 07 Nov 2018 10:30:08 GMT

←Older revision		Revision as of 10:30, 7 November 2018
Line 3:		Line 3:
	The entry 5od7 is ON HOLD		The entry 5od7 is ON HOLD

-	Authors: Schuetz, D.A., Richter, L., Amaral, M., Grandits, M., Musil, D., Graedler, U., Buchstaller, H.-P., Eggenweiler, H.-M., Frech, M., Ecker, G.F.	+	Authors: Schuetz, D.A., Richter, L., Amaral, M., Grandits, M., Musil, D., Graedler, U., Buchstaller, H.-P., Eggenweiler, H.-M., Frech, M., Ecker, G.F., Lehmann, M.

	Description: Hsp90 inhibitor desolvation as a rationale to steer on-rates and impact residence time		Description: Hsp90 inhibitor desolvation as a rationale to steer on-rates and impact residence time
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: ~~Frech~~, M]]	+	[[Category: Lehmann, M]]
-	~~[[Category: Ecker, G.F]]~~	+
-	~~[[Category: Musil, D]]~~	+
-	~~[[Category: Eggenweiler, H.-M]]~~	+
-	~~[[Category: Richter, L~~]]	+
	[[Category: Graedler, U]]		[[Category: Graedler, U]]
-	[[Category: ~~Grandits~~, M]]	+	[[Category: Frech, M]]
-	~~[[Category: Schuetz, D.A~~]]	+
	[[Category: Amaral, M]]		[[Category: Amaral, M]]
	[[Category: Buchstaller, H.-P]]		[[Category: Buchstaller, H.-P]]
		+	[[Category: Grandits, M]]
		+	[[Category: Eggenweiler, H.-M]]
		+	[[Category: Ecker, G.F]]
		+	[[Category: Schuetz, D.A]]
		+	[[Category: Richter, L]]
		+	[[Category: Musil, D]]

OCA: Protected "5od7" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 12:18:09 GMT

Protected "5od7" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:18, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5od7 is ON HOLD Authors: Schuetz, D.A., Richter, L., Amaral, M., Grandits, M., Musil, D., Graedler, U., Buchstaller, H.-P., Eggenweiler, H.-M., Frec...

OCA — Wed, 27 Sep 2017 12:18:08 GMT

New page: '''Unreleased structure''' The entry 5od7 is ON HOLD Authors: Schuetz, D.A., Richter, L., Amaral, M., Grandits, M., Musil, D., Graedler, U., Buchstaller, H.-P., Eggenweiler, H.-M., Frec...

New page

'''Unreleased structure'''

The entry 5od7 is ON HOLD

Authors: Schuetz, D.A., Richter, L., Amaral, M., Grandits, M., Musil, D., Graedler, U., Buchstaller, H.-P., Eggenweiler, H.-M., Frech, M., Ecker, G.F.

Description: Hsp90 inhibitor desolvation as a rationale to steer on-rates and impact residence time
[[Category: Unreleased Structures]]
[[Category: Frech, M]]
[[Category: Ecker, G.F]]
[[Category: Musil, D]]
[[Category: Eggenweiler, H.-M]]
[[Category: Richter, L]]
[[Category: Graedler, U]]
[[Category: Grandits, M]]
[[Category: Schuetz, D.A]]
[[Category: Amaral, M]]
[[Category: Buchstaller, H.-P]]