1osh - Revision history

OCA at 08:02, 14 February 2024

2024-02-14T08:02:46Z

←Older revision		Revision as of 08:02, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='1osh' size='340' side='right'caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='1osh' size='340' side='right'caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1osh]] 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=1OSH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1OSH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1osh]] 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=1OSH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OSH FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=FEX:METHYL+3-{3~~-[~~(CYCLOHEXYLCARBONYL){~~[~~4-(DIMETHYLAMINO)BIPHENYL-4-YL~~]~~METHYL}AMINO~~]~~PHENYL}ACRYLATE'>FEX</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]] 1.8Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~NR1H4 ([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=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene></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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [~~http~~://pdbe.org/1osh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1osh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1osh 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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [https://pdbe.org/1osh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [https://www.ebi.ac.uk/pdbsum/1osh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1osh ProSAT]</span></td></tr>
	</table>		</table>
	== 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>	+	[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1osh ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1osh ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The farnesoid X receptor (FXR) functions as a bile acid (BA) sensor coordinating cholesterol metabolism, lipid homeostasis, and absorption of dietary fats and vitamins. However, BAs are poor reagents for characterizing FXR functions due to multiple receptor independent properties. Accordingly, using combinatorial chemistry we evolved a small molecule agonist termed fexaramine with 100-fold increased affinity relative to natural compounds. Gene-profiling experiments conducted in hepatocytes with FXR-specific fexaramine versus the primary BA chenodeoxycholic acid (CDCA) produced remarkably distinct genomic targets. Highly diffracting cocrystals (1.78 A) of fexaramine bound to the ligand binding domain of FXR revealed the agonist sequestered in a 726 A(3) hydrophobic cavity and suggest a mechanistic basis for the initial step in the BA signaling pathway. The discovery of fexaramine will allow us to unravel the FXR genetic network from the BA network and selectively manipulate components of the cholesterol pathway that may be useful in treating cholesterol-related human diseases.
-
-	A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR.,Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, Rosenfeld JM, Alvarez JG, Noel JP, Nicolaou KC, Evans RM Mol Cell. 2003 Apr;11(4):1079-92. PMID:12718892<ref>PMID:12718892</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1osh" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Alvarez~~, J G.A~~]]	+	[[Category: Alvarez JGA]]
-	[[Category: Anisfeld~~, A M~~]]	+	[[Category: Anisfeld AM]]
-	[[Category: Bowman~~, M E~~]]	+	[[Category: Bowman ME]]
-	[[Category: Downes, M]]	+	[[Category: Downes M]]
-	[[Category: Edwards~~, P A~~]]	+	[[Category: Edwards PA]]
-	[[Category: Evans~~, R M~~]]	+	[[Category: Evans RM]]
-	[[Category: Ferrer, J L]]	+	[[Category: Ferrer J-L]]
-	[[Category: Hogenesch~~, J B~~]]	+	[[Category: Hogenesch JB]]
-	[[Category: Hughes, R]]	+	[[Category: Hughes R]]
-	[[Category: Kast-Woelbern~~, H R~~]]	+	[[Category: Kast-Woelbern HR]]
-	[[Category: Nicolaou~~, K C~~]]	+	[[Category: Nicolaou KC]]
-	[[Category: Noel~~, J P~~]]	+	[[Category: Noel JP]]
-	[[Category: Roecker~~, A J~~]]	+	[[Category: Roecker AJ]]
-	[[Category: Rosenfeld~~, J M~~]]	+	[[Category: Rosenfeld JM]]
-	[[Category: Verdecia~~, M A]]~~	+	[[Category: Verdecia MA]]
-	~~[[Category: Ligand binding domain]]~~	+
-	~~[[Category: Nuclear receptor]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 07:14, 9 December 2020

2020-12-09T07:14:36Z

←Older revision		Revision as of 07:14, 9 December 2020
Line 1:		Line 1:

	==A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR==		==A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR==
-	<StructureSection load='1osh' size='340' side='right' caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='1osh' size='340' side='right'caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1osh]] 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=1OSH OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1OSH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1osh]] 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=1OSH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1OSH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://pdbe.org/1osh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1osh ProSAT]</span></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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://pdbe.org/1osh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1osh ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 29:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 1osh" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1osh" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bile acid receptor 3D structures\|Bile acid receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 34:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Alvarez, J G.A]]		[[Category: Alvarez, J G.A]]
	[[Category: Anisfeld, A M]]		[[Category: Anisfeld, A M]]

OCA at 07:35, 15 February 2018

2018-02-15T07:35:03Z

←Older revision		Revision as of 07:35, 15 February 2018
Line 1:		Line 1:
		+
	==A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR==		==A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR==
	<StructureSection load='1osh' size='340' side='right' caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='1osh' size='340' side='right' caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://pdbe.org/1osh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum]</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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://pdbe.org/1osh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1osh ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/os/1osh_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/os/1osh_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 28:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 1osh" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1osh" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Bile acid receptor\|Bile acid receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:56, 8 February 2016

2016-02-08T12:56:37Z

←Older revision		Revision as of 12:56, 8 February 2016
Line 17:		Line 17:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1osh ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 11:48, 10 September 2015

2015-09-10T11:48:01Z

←Older revision		Revision as of 11:48, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1osh' size='340' side='right' caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='1osh' size='340' side='right' caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1osh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1osh]] 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=1OSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum]</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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://pdbe.org/1osh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 27:		Line 27:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1osh" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Alvarez, J G.A]]		[[Category: Alvarez, J G.A]]
	[[Category: Anisfeld, A M]]		[[Category: Anisfeld, A M]]

OCA at 23:28, 24 December 2014

2014-12-24T23:28:22Z

←Older revision		Revision as of 23:28, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1osh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSH FirstGlance]. <br>		<table><tr><td colspan='2'>[[1osh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSH FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum]</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=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Alvarez, J G.A.]]	+	[[Category: Alvarez, J G.A]]
-	[[Category: Anisfeld, A M.]]	+	[[Category: Anisfeld, A M]]
-	[[Category: Bowman, M E.]]	+	[[Category: Bowman, M E]]
-	[[Category: Downes, M.]]	+	[[Category: Downes, M]]
-	[[Category: Edwards, P A.]]	+	[[Category: Edwards, P A]]
-	[[Category: Evans, R M.]]	+	[[Category: Evans, R M]]
-	[[Category: Ferrer, J L.]]	+	[[Category: Ferrer, J L]]
-	[[Category: Hogenesch, J B.]]	+	[[Category: Hogenesch, J B]]
-	[[Category: Hughes, R.]]	+	[[Category: Hughes, R]]
-	[[Category: Kast-Woelbern, H R.]]	+	[[Category: Kast-Woelbern, H R]]
-	[[Category: Nicolaou, K C.]]	+	[[Category: Nicolaou, K C]]
-	[[Category: Noel, J P.]]	+	[[Category: Noel, J P]]
-	[[Category: Roecker, A J.]]	+	[[Category: Roecker, A J]]
-	[[Category: Rosenfeld, J M.]]	+	[[Category: Rosenfeld, J M]]
-	[[Category: Verdecia, M A.]]	+	[[Category: Verdecia, M A]]
	[[Category: Ligand binding domain]]		[[Category: Ligand binding domain]]
	[[Category: Nuclear receptor]]		[[Category: Nuclear receptor]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA at 20:57, 28 September 2014

2014-09-28T20:57:18Z

←Older revision		Revision as of 20:57, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1osh.~~png~~\|~~left~~\|200px]]	+	==A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR==
		+	<StructureSection load='1osh' size='340' side='right' caption='[[1osh]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1osh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSH FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEX:METHYL+3-{3-[(CYCLOHEXYLCARBONYL){[4-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1osh RCSB], [http://www.ebi.ac.uk/pdbsum/1osh PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/os/1osh_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The farnesoid X receptor (FXR) functions as a bile acid (BA) sensor coordinating cholesterol metabolism, lipid homeostasis, and absorption of dietary fats and vitamins. However, BAs are poor reagents for characterizing FXR functions due to multiple receptor independent properties. Accordingly, using combinatorial chemistry we evolved a small molecule agonist termed fexaramine with 100-fold increased affinity relative to natural compounds. Gene-profiling experiments conducted in hepatocytes with FXR-specific fexaramine versus the primary BA chenodeoxycholic acid (CDCA) produced remarkably distinct genomic targets. Highly diffracting cocrystals (1.78 A) of fexaramine bound to the ligand binding domain of FXR revealed the agonist sequestered in a 726 A(3) hydrophobic cavity and suggest a mechanistic basis for the initial step in the BA signaling pathway. The discovery of fexaramine will allow us to unravel the FXR genetic network from the BA network and selectively manipulate components of the cholesterol pathway that may be useful in treating cholesterol-related human diseases.

-	~~{{STRUCTURE_1osh\| PDB=1osh \| SCENE= }}~~	+	A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR.,Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, Rosenfeld JM, Alvarez JG, Noel JP, Nicolaou KC, Evans RM Mol Cell. 2003 Apr;11(4):1079-92. PMID:12718892<ref>PMID:12718892</ref>

-	~~===A Chemical~~, ~~Genetic, and Structural Analysis~~ of the ~~nuclear bile acid receptor FXR===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_12718892}}~~	+	==See Also==
-		+	*[[Bile acid receptor\|Bile acid receptor]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~1osh~~]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:012718892<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Alvarez, J G.A.]]		[[Category: Alvarez, J G.A.]]

OCA: Protected "1osh" [edit=sysop:move=sysop]

2012-12-12T21:58:38Z

Protected "1osh" [edit=sysop:move=sysop]

←Older revision

Revision as of 21:58, 12 December 2012

OCA at 21:58, 12 December 2012

2012-12-12T21:58:35Z

←Older revision		Revision as of 21:58, 12 December 2012
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-	{{Seed}}
	[[Image:1osh.png\|left\|200px]]		[[Image:1osh.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1osh", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_1osh\| PDB=1osh \| SCENE= }}		{{STRUCTURE_1osh\| PDB=1osh \| SCENE= }}

	===A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR===		===A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_12718892}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 12718892 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_12718892}}		{{ABSTRACT_PUBMED_12718892}}

	==About this Structure==		==About this Structure==
-	~~1OSH~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA].	+	[[1osh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~12718892~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012718892</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Alvarez, J G.A.]]		[[Category: Alvarez, J G.A.]]
Line 42:		Line 30:
	[[Category: Ligand binding domain]]		[[Category: Ligand binding domain]]
	[[Category: Nuclear receptor]]		[[Category: Nuclear receptor]]
-		+	[[Category: Transcription]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Mon Feb 16 22:10:40 2009''~~	+

OCA at 20:10, 16 February 2009

2009-02-16T20:10:41Z

←Older revision		Revision as of 20:10, 16 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	1OSH is a ~~[[Single protein]]~~ structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA].	+	1OSH is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA].

	==Reference==		==Reference==
-	A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR., Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, Rosenfeld JM, Alvarez JG, Noel JP, Nicolaou KC, Evans RM, Mol Cell. 2003 Apr;11(4):1079-92. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/12718892 12718892]~~	+	<ref group="xtra">PMID:12718892</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Single protein]]
	[[Category: Alvarez, J G.A.]]		[[Category: Alvarez, J G.A.]]
	[[Category: Anisfeld, A M.]]		[[Category: Anisfeld, A M.]]
Line 44:		Line 43:
	[[Category: Nuclear receptor]]		[[Category: Nuclear receptor]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon ~~Jul 28 03~~:12:~~42 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 22:10:40 2009''