OCA at 14:44, 18 October 2023

OCA — Wed, 18 Oct 2023 14:44:43 GMT

←Older revision		Revision as of 14:44, 18 October 2023
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-	====	+	==Glucocorticoid Receptor DNA binding domain in complex with methylated precursor for a modern recognition element (methylated pre-GBS)==
-	<StructureSection load='6x6e' size='340' side='right'caption='[[6x6e]]' scene=''>	+	<StructureSection load='6x6e' size='340' side='right'caption='[[6x6e]], [[Resolution\|resolution]] 2.00Å' 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 [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6x6e]] is a 4 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=6X6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X6E FirstGlance]. <br>
-	</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=6x6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x6e OCA], [https://pdbe.org/6x6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x6e RCSB], [https://www.ebi.ac.uk/pdbsum/6x6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x6e 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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6x6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x6e OCA], [https://pdbe.org/6x6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x6e RCSB], [https://www.ebi.ac.uk/pdbsum/6x6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x6e ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:[https://omim.org/entry/138040 138040]; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.<ref>PMID:12050230</ref> <ref>PMID:1704018</ref> <ref>PMID:7683692</ref> <ref>PMID:11589680</ref> <ref>PMID:11701741</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation.<ref>PMID:21664385</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The most common form of DNA methylation involves the addition of a methyl group to a cytosine base in the context of a cytosine-phosphate-guanine (CpG) dinucleotide. Genomes from more primitive organisms are more abundant in CpG sites that, through the process of methylation, deamination and subsequent mutation to thymine-phosphate-guanine (TpG) sites, can produce new transcription factor binding sites. Here, we examined the evolutionary history of the over 36 000 glucocorticoid receptor (GR) consensus binding motifs in the human genome and identified a subset of them in regulatory regions that arose via a deamination and subsequent mutation event. GR can bind to both unmodified and methylated pre-GR binding sequences (GBSs) that contain a CpG site. Our structural analyses show that CpG methylation in a pre-GBS generates a favorable interaction with Arg447 mimicking that made with a TpG in a GBS. This methyl-specific recognition arose 420 million years ago and was conserved during the evolution of GR and likely helps fix the methylation on the relevant cytosines. Our study provides the first genetic, biochemical and structural evidence of high-affinity binding for the likely evolutionary precursor of extant TpG-containing GBS.
		+
		+	Structural basis for glucocorticoid receptor recognition of both unmodified and methylated binding sites, precursors of a modern recognition element.,Liu X, Weikum ER, Tilo D, Vinson C, Ortlund EA Nucleic Acids Res. 2021 Sep 7;49(15):8923-8933. doi: 10.1093/nar/gkab605. PMID:34289059<ref>PMID:34289059</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6x6e" 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: Liu X]]
		+	[[Category: Ortlund EA]]

OCA at 14:32, 2 June 2021

OCA — Wed, 02 Jun 2021 14:32:31 GMT

←Older revision		Revision as of 14:32, 2 June 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6x6e ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6x6e' size='340' side='right'caption='[[6x6e]]' scene=''>
-	~~Authors~~:	+	== 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 [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=6x6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x6e OCA], [https://pdbe.org/6x6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x6e RCSB], [https://www.ebi.ac.uk/pdbsum/6x6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x6e ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 10:41, 8 July 2020

OCA — Wed, 08 Jul 2020 10:41:19 GMT

←Older revision		Revision as of 10:41, 8 July 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6x6e is ON HOLD	+	The entry 6x6e is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6x6e" [edit=sysop:move=sysop]

OCA — Wed, 03 Jun 2020 05:15:47 GMT

Protected "6x6e" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:15, 3 June 2020

OCA: New page: '''Unreleased structure''' The entry 6x6e is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 03 Jun 2020 05:15:46 GMT

New page: '''Unreleased structure''' The entry 6x6e is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6x6e is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6x6e - Revision history

OCA at 14:44, 18 October 2023

OCA at 14:32, 2 June 2021

OCA at 10:41, 8 July 2020

OCA: Protected "6x6e" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6x6e is ON HOLD Authors: Description: Category: Unreleased Structures