5wzx - Revision history

OCA at 07:52, 22 November 2023

OCA — Wed, 22 Nov 2023 07:52:14 GMT

←Older revision		Revision as of 07:52, 22 November 2023
Line 1:		Line 1:

	==Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR==		==Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR==
-	<StructureSection load='5wzx' size='340' side='right' caption='[[5wzx]], [[Resolution\|resolution]] 2.95Å' scene=''>	+	<StructureSection load='5wzx' size='340' side='right'caption='[[5wzx]], [[Resolution\|resolution]] 2.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wzx]] is a 4 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=5WZX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WZX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wzx]] 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=5WZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WZX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7VX:(4aR,6aR,6aS,6bS,8aS,9R,12aR,14bR)-2,2,6a,6b,9,12a-hexamethyl-10-oxidanylidene-1,3,4,5,6,6a,7,8,8a,9,11,12,13,14b-tetradecahydropicene-4a-carboxylic+acid'>7VX</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</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]] 2.95Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4, BAR, FXR, HRR1, RIP14 ([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=7VX:(4aR,6aR,6aS,6bS,8aS,9R,12aR,14bR)-2,2,6a,6b,9,12a-hexamethyl-10-oxidanylidene-1,3,4,5,6,6a,7,8,8a,9,11,12,13,14b-tetradecahydropicene-4a-carboxylic+acid'>7VX</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</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=5wzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wzx OCA], [~~http~~://pdbe.org/5wzx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wzx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wzx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wzx 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=5wzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wzx OCA], [https://pdbe.org/5wzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wzx RCSB], [https://www.ebi.ac.uk/pdbsum/5wzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wzx ProSAT]</span></td></tr>
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NR1H4_HUMAN NR1H4_HUMAN]] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.<ref>PMID:10334992</ref> <ref>PMID:10334993</ref> <ref>PMID:12815072</ref> <ref>PMID:15471871</ref> <ref>PMID:12718892</ref> <ref>PMID:18621523</ref> <ref>PMID:19410460</ref> <ref>PMID:19586769</ref> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>	+	[https://www.uniprot.org/uniprot/NR1H4_HUMAN NR1H4_HUMAN] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.<ref>PMID:10334992</ref> <ref>PMID:10334993</ref> <ref>PMID:12815072</ref> <ref>PMID:15471871</ref> <ref>PMID:12718892</ref> <ref>PMID:18621523</ref> <ref>PMID:19410460</ref> <ref>PMID:19586769</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5wzx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5wzx" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bile acid receptor 3D structures\|Bile acid receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Li, Y~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Lu,~~ Y]]	+	[[Category: Li Y]]
-	[[Category: ~~Fxr ligand]]~~	+	[[Category: Lu Y]]
-	~~[[Category: Transcription~~]]	+

OCA at 08:18, 17 January 2018

OCA — Wed, 17 Jan 2018 08:18:06 GMT

←Older revision		Revision as of 08:18, 17 January 2018
Line 3:		Line 3:
	<StructureSection load='5wzx' size='340' side='right' caption='[[5wzx]], [[Resolution\|resolution]] 2.95Å' scene=''>		<StructureSection load='5wzx' size='340' side='right' caption='[[5wzx]], [[Resolution\|resolution]] 2.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wzx]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WZX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wzx]] is a 4 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=5WZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WZX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7VX:(4aR,6aR,6aS,6bS,8aS,9R,12aR,14bR)-2,2,6a,6b,9,12a-hexamethyl-10-oxidanylidene-1,3,4,5,6,6a,7,8,8a,9,11,12,13,14b-tetradecahydropicene-4a-carboxylic+acid'>7VX</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7VX:(4aR,6aR,6aS,6bS,8aS,9R,12aR,14bR)-2,2,6a,6b,9,12a-hexamethyl-10-oxidanylidene-1,3,4,5,6,6a,7,8,8a,9,11,12,13,14b-tetradecahydropicene-4a-carboxylic+acid'>7VX</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4, BAR, FXR, HRR1, RIP14 ([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=5wzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wzx OCA], [http://pdbe.org/5wzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wzx RCSB], [http://www.ebi.ac.uk/pdbsum/5wzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wzx 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=5wzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wzx OCA], [http://pdbe.org/5wzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wzx RCSB], [http://www.ebi.ac.uk/pdbsum/5wzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wzx ProSAT]</span></td></tr>
	</table>		</table>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Li, Y]]		[[Category: Li, Y]]
	[[Category: Lu, Y]]		[[Category: Lu, Y]]
	[[Category: Fxr ligand]]		[[Category: Fxr ligand]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA at 05:49, 3 January 2018

OCA — Wed, 03 Jan 2018 05:49:47 GMT

←Older revision		Revision as of 05:49, 3 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5wzx is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR==
		+	<StructureSection load='5wzx' size='340' side='right' caption='[[5wzx]], [[Resolution\|resolution]] 2.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5wzx]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WZX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7VX:(4aR,6aR,6aS,6bS,8aS,9R,12aR,14bR)-2,2,6a,6b,9,12a-hexamethyl-10-oxidanylidene-1,3,4,5,6,6a,7,8,8a,9,11,12,13,14b-tetradecahydropicene-4a-carboxylic+acid'>7VX</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</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=5wzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wzx OCA], [http://pdbe.org/5wzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wzx RCSB], [http://www.ebi.ac.uk/pdbsum/5wzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wzx ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NR1H4_HUMAN NR1H4_HUMAN]] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.<ref>PMID:10334992</ref> <ref>PMID:10334993</ref> <ref>PMID:12815072</ref> <ref>PMID:15471871</ref> <ref>PMID:12718892</ref> <ref>PMID:18621523</ref> <ref>PMID:19410460</ref> <ref>PMID:19586769</ref> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (GPBAR1) are two important bile acid (BA) receptors. As non-BAs drug template for GPBAR1, none of the natural oleanane-type triterpenes have been reported as FXR ligands, despite FXR and GPBAR1 having similar binding pockets for BAs. Here, we report the natural triterpene hedragonic acid that has been isolated from the stem and root of Celastrus orbiculatus Thunb. (COT) as an effective agonist for FXR. Both biochemical amplified luminescent proximity homogeneous assay and cell-based reporter assays showed that hedragonic acid regulated the transcriptional activity of FXR. Circular dichroism spectroscopy further suggested the conformational changes of FXR upon the binding of hedragonic acid. Interestingly, the crystal structure of hedragonic acid-bound FXR revealed a unique binding mode with hedragonic acid occupying a novel binding pocket different from the classic binding position. The structural comparison between hedragonic acid-bound FXR and oleanolic acid-bound GPBAR1 explained the molecular basis for the selectivity of oleanane-type triterpenes for FXR. Moreover, hedragonic acid treatment protected mice from liver injury induced by acetaminophen overdose and decreased hepatic inflammatory responses in an FXR-dependent manner, suggesting that hedragonic acid might be one of the major components of COT for its multifunctional pharmaceutical uses. In conclusion, our results provide novel structure templates for drug design based on natural triterpenes by targeting FXR and/or GPBAR1 with pharmaceutical values.

-	~~Authors:~~ Lu, Y., Li, Y.	+	Identification of an Oleanane-Type Triterpene Hedragonic Acid as a Novel Farnesoid X Receptor Ligand with Liver Protective Effects and Anti-inflammatory Activity.,Lu Y, Zheng W, Lin S, Guo F, Zhu Y, Wei Y, Liu X, Jin S, Jin L, Li Y Mol Pharmacol. 2018 Feb;93(2):63-72. doi: 10.1124/mol.117.109900. Epub 2017 Nov, 21. PMID:29162643<ref>PMID:29162643</ref>

-	~~Description: Structural basis for~~ a ~~pentacyclic oleanane-type triterpenoid as a ligand~~ of ~~FXR~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5wzx" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Li, Y]]		[[Category: Li, Y]]
	[[Category: Lu, Y]]		[[Category: Lu, Y]]
		+	[[Category: Fxr ligand]]
		+	[[Category: Transcription]]

OCA at 15:13, 27 September 2017

OCA — Wed, 27 Sep 2017 15:13:07 GMT

←Older revision		Revision as of 15:13, 27 September 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wzx is ON HOLD	+	The entry 5wzx is ON HOLD until Paper Publication

	Authors: Lu, Y., Li, Y.		Authors: Lu, Y., Li, Y.
Line 7:		Line 7:
	Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR		Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Lu, Y]]
	[[Category: Li, Y]]		[[Category: Li, Y]]
		+	[[Category: Lu, Y]]

OCA at 20:02, 15 March 2017

OCA — Wed, 15 Mar 2017 20:02:00 GMT

←Older revision		Revision as of 20:02, 15 March 2017
Line 7:		Line 7:
	Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR		Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Li, Y]]
	[[Category: Lu, Y]]		[[Category: Lu, Y]]
		+	[[Category: Li, Y]]

OCA at 17:07, 1 February 2017

OCA — Wed, 01 Feb 2017 17:07:28 GMT

←Older revision		Revision as of 17:07, 1 February 2017
Line 3:		Line 3:
	The entry 5wzx is ON HOLD		The entry 5wzx is ON HOLD

-	Authors: Lu, Yi, Li, ~~Yong~~	+	Authors: Lu, Y., Li, Y.

	Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR		Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Lu, ~~Yi, Li, Yong~~]]	+	[[Category: Li, Y]]
		+	[[Category: Lu, Y]]

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

OCA — Wed, 25 Jan 2017 22:39:01 GMT

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

←Older revision

Revision as of 22:39, 25 January 2017

OCA: New page: '''Unreleased structure''' The entry 5wzx is ON HOLD Authors: Lu, Yi, Li, Yong Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR [[Category:...

OCA — Wed, 25 Jan 2017 22:38:59 GMT

New page: '''Unreleased structure''' The entry 5wzx is ON HOLD Authors: Lu, Yi, Li, Yong Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR [[Category:...

New page

'''Unreleased structure'''

The entry 5wzx is ON HOLD

Authors: Lu, Yi, Li, Yong

Description: Structural basis for a pentacyclic oleanane-type triterpenoid as a ligand of FXR
[[Category: Unreleased Structures]]
[[Category: Lu, Yi, Li, Yong]]