OCA at 12:18, 1 February 2024

OCA — Thu, 01 Feb 2024 12:18:15 GMT

←Older revision		Revision as of 12:18, 1 February 2024
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	==Crystal structure of the hPXR-LBD in complex with clotrimazole==		==Crystal structure of the hPXR-LBD in complex with clotrimazole==
-	<StructureSection load='7axa' size='340' side='right'caption='[[7axa]]' scene=''>	+	<StructureSection load='7axa' size='340' side='right'caption='[[7axa]], [[Resolution\|resolution]] 2.26Å' 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=7AXA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7AXA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7axa]] 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=7AXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AXA 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=7axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7axa OCA], [~~http~~://pdbe.org/7axa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7axa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7axa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7axa 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]] 2.26Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL6:1-[(2-CHLOROPHENYL)(DIPHENYL)METHYL]-1H-IMIDAZOLE'>CL6</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=7axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7axa OCA], [https://pdbe.org/7axa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7axa RCSB], [https://www.ebi.ac.uk/pdbsum/7axa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7axa ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/NR1I2_HUMAN NR1I2_HUMAN] Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.<ref>PMID:9727070</ref> <ref>PMID:11668216</ref> <ref>PMID:11297522</ref> <ref>PMID:19297428</ref> <ref>PMID:12578355</ref> <ref>PMID:18768384</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Humans are chronically exposed to mixtures of xenobiotics referred to as endocrine-disrupting chemicals (EDCs). A vast body of literature links exposure to these chemicals with increased incidences of reproductive, metabolic, or neurological disorders. Moreover, recent data demonstrate that, when used in combination, chemicals have outcomes that cannot be predicted from their individual behavior. In its heterodimeric form with the retinoid X receptor (RXR), the pregnane X receptor (PXR) plays an essential role in controlling the mammalian xenobiotic response and mediates both beneficial and detrimental effects. Our previous work shed light on a mechanism by which a binary mixture of xenobiotics activates PXR in a synergistic fashion. Structural analysis revealed that mutual stabilization of the compounds within the ligand-binding pocket of PXR accounts for the enhancement of their binding affinity. In order to identify and characterize additional active mixtures, we combined a set of cell-based, biophysical, structural, and in vivo approaches. Our study reveals features that confirm the binding promiscuity of this receptor and its ability to accommodate bipartite ligands. We reveal previously unidentified binding mechanisms involving dynamic structural transitions and covalent coupling and report four binary mixtures eliciting graded synergistic activities. Last, we demonstrate that the robust activity obtained with two synergizing PXR ligands can be enhanced further in the presence of RXR environmental ligands. Our study reveals insights as to how low-dose EDC mixtures may alter physiology through interaction with RXR-PXR and potentially several other nuclear receptor heterodimers.
		+
		+	Mechanistic insights into the synergistic activation of the RXR-PXR heterodimer by endocrine disruptor mixtures.,Delfosse V, Huet T, Harrus D, Granell M, Bourguet M, Gardia-Parege C, Chiavarina B, Grimaldi M, Le Mevel S, Blanc P, Huang D, Gruszczyk J, Demeneix B, Cianferani S, Fini JB, Balaguer P, Bourguet W Proc Natl Acad Sci U S A. 2021 Jan 5;118(1). pii: 2020551118. doi:, 10.1073/pnas.2020551118. PMID:33361153<ref>PMID:33361153</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7axa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Pregnane X receptor 3D structures\|Pregnane X receptor 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Blanc P]]		[[Category: Blanc P]]

OCA at 05:53, 20 January 2021

OCA — Wed, 20 Jan 2021 05:53:14 GMT

←Older revision		Revision as of 05:53, 20 January 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7axa is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of the hPXR-LBD in complex with clotrimazole==
-		+	<StructureSection load='7axa' size='340' side='right'caption='[[7axa]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AXA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AXA FirstGlance]. <br>
-	~~Description~~:	+	</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=7axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7axa OCA], [http://pdbe.org/7axa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7axa RCSB], [http://www.ebi.ac.uk/pdbsum/7axa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7axa ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Blanc P]]
		+	[[Category: Bourguet W]]
		+	[[Category: Delfosse V]]
		+	[[Category: Granell M]]

OCA: Protected "7axa" [edit=sysop:move=sysop]

OCA — Wed, 18 Nov 2020 07:55:24 GMT

Protected "7axa" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:55, 18 November 2020

OCA: New page: '''Unreleased structure''' The entry 7axa is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 18 Nov 2020 07:55:23 GMT

New page: '''Unreleased structure''' The entry 7axa is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7axa is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]

7axa - Revision history

OCA at 12:18, 1 February 2024

OCA at 05:53, 20 January 2021

OCA: Protected "7axa" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7axa is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures