6w9k - Revision history

OCA at 14:19, 18 October 2023

2023-10-18T14:19:17Z

←Older revision		Revision as of 14:19, 18 October 2023
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-	====	+	==Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with Prednisolone and PGC1a coregulator fragment==
-	<StructureSection load='6w9k' size='340' side='right'caption='[[6w9k]]' scene=''>	+	<StructureSection load='6w9k' size='340' side='right'caption='[[6w9k]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6w9k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W9K FirstGlance]. <br>
-	</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=6w9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9k OCA], [~~http~~://pdbe.org/6w9k PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6w9k RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6w9k PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9k ProSAT]</span></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]] 1.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TUA:prednisolone'>TUA</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=6w9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9k OCA], [https://pdbe.org/6w9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w9k RCSB], [https://www.ebi.ac.uk/pdbsum/6w9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9k ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A1X8XLE9_9ZZZZ A0A1X8XLE9_9ZZZZ]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Duchenne muscular dystrophy is a genetic disorder that shows chronic and progressive damage to skeletal and cardiac muscle leading to premature death. Antiinflammatory corticosteroids targeting the glucocorticoid receptor (GR) are the current standard of care but drive adverse side effects such as deleterious bone loss. Through subtle modification to a steroidal backbone, a recently developed drug, vamorolone, appears to preserve beneficial efficacy but with significantly reduced side effects. We use combined structural, biophysical, and biochemical approaches to show that loss of a receptor-ligand hydrogen bond drives these remarkable therapeutic effects. Moreover, vamorolone uniformly weakens coactivator associations but not corepressor associations, implicating partial agonism as the main driver of its dissociative properties. Additionally, we identify a critical and evolutionarily conserved intramolecular network connecting the ligand to the coregulator binding surface. Interruption of this allosteric network by vamorolone selectively reduces GR-driven transactivation while leaving transrepression intact. Our results establish a mechanistic understanding of how vamorolone reduces side effects, guiding the future design of partial agonists as selective GR modulators with an improved therapeutic index.
		+
		+	Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment.,Liu X, Wang Y, Gutierrez JS, Damsker JM, Nagaraju K, Hoffman EP, Ortlund EA Proc Natl Acad Sci U S A. 2020 Sep 29;117(39):24285-24293. doi: , 10.1073/pnas.2006890117. Epub 2020 Sep 11. PMID:32917814<ref>PMID:32917814</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6w9k" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Glucocorticoid receptor 3D structures\|Glucocorticoid receptor 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Synthetic construct]]
		+	[[Category: Liu X]]
		+	[[Category: Ortlund EA]]

OCA at 07:22, 4 November 2020

2020-11-04T07:22:31Z

←Older revision		Revision as of 07:22, 4 November 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6w9k ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6w9k' size='340' side='right'caption='[[6w9k]]' scene=''>
-	~~Authors~~: ~~Liu, X~~.~~, Ortlund, E~~.A.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: Structure of~~ the ~~Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with Prednisolone and PGC1a coregulator fragment~~	+	</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=6w9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9k OCA], [http://pdbe.org/6w9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w9k RCSB], [http://www.ebi.ac.uk/pdbsum/6w9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9k ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Liu, X~~]]	+	__TOC__
-	[[Category: ~~Ortlund, E.A~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 03:59, 13 May 2020

2020-05-13T03:59:05Z

←Older revision		Revision as of 03:59, 13 May 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6w9k is ON HOLD	+	The entry 6w9k is ON HOLD until Paper Publication

	Authors: Liu, X., Ortlund, E.A.		Authors: Liu, X., Ortlund, E.A.

OCA: Protected "6w9k" [edit=sysop:move=sysop]

2020-04-01T07:31:06Z

Protected "6w9k" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:31, 1 April 2020

OCA: New page: '''Unreleased structure''' The entry 6w9k is ON HOLD Authors: Liu, X., Ortlund, E.A. Description: Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex ...

2020-04-01T07:31:05Z

New page: '''Unreleased structure''' The entry 6w9k is ON HOLD Authors: Liu, X., Ortlund, E.A. Description: Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex ...

New page

'''Unreleased structure'''

The entry 6w9k is ON HOLD

Authors: Liu, X., Ortlund, E.A.

Description: Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with Prednisolone and PGC1a coregulator fragment
[[Category: Unreleased Structures]]
[[Category: Liu, X]]
[[Category: Ortlund, E.A]]