3oki - Revision history

OCA at 11:17, 21 February 2024

2024-02-21T11:17:08Z

← Older revision		Revision as of 11:17, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3oki' size='340' side='right'caption='[[3oki]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3oki' size='340' side='right'caption='[[3oki]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3oki]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OKI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3oki]] 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=3OKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OKI FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=OKI:(2S)-2~~-[~~2-(4-CHLOROPHENYL)-1H-BENZIMIDAZOL-1-YL~~]~~-N,~~2~~-DICYCLOHEXYLETHANAMIDE'>OKI</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]] 2Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;'>~~[~~[3okh\|3okh]~~], ~~[[3olf\|3olf]], [[3omk\|3omk]], [[3omm\|3omm]], [[3oof\|3oof]], [[3ook\|3ook]]</div></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OKI:(2S)-2-[2-(4-CHLOROPHENYL)-1H-BENZIMIDAZOL-1-YL]-N,2-DICYCLOHEXYLETHANAMIDE'>OKI</scene></td></tr>
	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</b>~~</td><td class="sblockDat">NR1H4, HCG_20893 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3oki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oki OCA], [https://pdbe.org/3oki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oki RCSB], [https://www.ebi.ac.uk/pdbsum/3oki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oki 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=3oki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oki OCA], [https://pdbe.org/3oki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oki RCSB], [https://www.ebi.ac.uk/pdbsum/3oki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oki ProSAT]</span></td></tr>
	</table>		</table>
	~~== Disease ==~~
	[[https://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.
	== Function ==		== Function ==
	[[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> [[https://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</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;">~~
	~~== Publication Abstract from PubMed ==~~
	Herein we describe the synthesis and structure activity relationship of a new class of FXR agonists identified from a high-throughput screening campaign. Further optimization of the original hits led to molecules that were highly active in an LDL-receptor KO model for dyslipidemia. The most promising candidate is discussed in more detail.

	Discovery of novel and orally active FXR agonists for the potential treatment of dyslipidemia & diabetes.,Richter HG, Benson GM, Blum D, Chaput E, Feng S, Gardes C, Grether U, Hartman P, Kuhn B, Martin RE, Plancher JM, Rudolph MG, Schuler F, Taylor S, Bleicher KH Bioorg Med Chem Lett. 2011 Jan 1;21(1):191-4. Epub 2010 Nov 12. PMID:21134747<ref>PMID:21134747</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3oki" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==
Line 29:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Rudolph~~, M G]]~~		[[Category: Rudolph MG]]
	~~[[Category: Bile acid]]~~
	~~[[Category: Cholesterol]]~~
	~~[[Category: Coactivator]]~~
	~~[[Category: Dna-binding]]~~
	~~[[Category: Fxr alternative splicing]]~~
	~~[[Category: Hormone receptor]]~~
	~~[[Category: Ligand binding domain transcription regulation]]~~
	~~[[Category: Nuclear receptor]]~~
	~~[[Category: Nucleus]]~~
	~~[[Category: Receptor]]~~
	~~[[Category: Transcription~~]]

OCA at 10:46, 18 May 2022

2022-05-18T10:46:43Z

← Older revision		Revision as of 10:46, 18 May 2022
Line 1:		Line 1:

	==Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide==		==Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide==
	<StructureSection load='3oki' size='340' side='right' caption='[[3oki]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3oki' size='340' side='right'caption='[[3oki]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3oki]] 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=3OKI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3OKI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3oki]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OKI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OKI:(2S)-2-[2-(4-CHLOROPHENYL)-1H-BENZIMIDAZOL-1-YL]-N,2-DICYCLOHEXYLETHANAMIDE'>OKI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OKI:(2S)-2-[2-(4-CHLOROPHENYL)-1H-BENZIMIDAZOL-1-YL]-N,2-DICYCLOHEXYLETHANAMIDE'>OKI</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3okh\|3okh]], [[3olf\|3olf]], [[3omk\|3omk]], [[3omm\|3omm]], [[3oof\|3oof]], [[3ook\|3ook]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3okh\|3okh]], [[3olf\|3olf]], [[3omk\|3omk]], [[3omm\|3omm]], [[3oof\|3oof]], [[3ook\|3ook]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4, HCG_20893 ([~~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, HCG_20893 ([https://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=3oki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oki OCA], [~~http~~://pdbe.org/3oki PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3oki RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3oki PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3oki 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=3oki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oki OCA], [https://pdbe.org/3oki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oki RCSB], [https://www.ebi.ac.uk/pdbsum/3oki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oki ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.		[[https://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.
	== 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/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</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> [[https://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 24:

	==See Also==		==See Also==
	*[[Bile acid receptor\|Bile acid receptor]]		*[[Bile acid receptor 3D structures\|Bile acid receptor 3D structures]]
	*[[Hormone\|Hormone]]
	== References ==		== References ==
	<references/>		<references/>
Line 31:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Rudolph, M G]]		[[Category: Rudolph, M G]]
	[[Category: Bile acid]]		[[Category: Bile acid]]

OCA at 08:01, 4 August 2016

2016-08-04T08:01:44Z

← Older revision		Revision as of 08:01, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide==		==Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide==
	<StructureSection load='3oki' size='340' side='right' caption='[[3oki]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3oki' size='340' side='right' caption='[[3oki]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3oki]] is a 4 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=3OKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OKI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3oki]] 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=3OKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OKI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OKI:(2S)-2-[2-(4-CHLOROPHENYL)-1H-BENZIMIDAZOL-1-YL]-N,2-DICYCLOHEXYLETHANAMIDE'>OKI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OKI:(2S)-2-[2-(4-CHLOROPHENYL)-1H-BENZIMIDAZOL-1-YL]-N,2-DICYCLOHEXYLETHANAMIDE'>OKI</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3okh\|3okh]], [[3olf\|3olf]], [[3omk\|3omk]], [[3omm\|3omm]], [[3oof\|3oof]], [[3ook\|3ook]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3okh\|3okh]], [[3olf\|3olf]], [[3omk\|3omk]], [[3omm\|3omm]], [[3oof\|3oof]], [[3ook\|3ook]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4, HCG_20893 ([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, HCG_20893 ([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=3oki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oki OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oki RCSB], [http://www.ebi.ac.uk/pdbsum/3oki 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=3oki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oki OCA], [http://pdbe.org/3oki PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3oki RCSB], [http://www.ebi.ac.uk/pdbsum/3oki PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3oki ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 3oki" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Rudolph, M G]]		[[Category: Rudolph, M G]]
	[[Category: Bile acid]]		[[Category: Bile acid]]

OCA at 07:07, 19 December 2014

2014-12-19T07:07:43Z

← Older revision		Revision as of 07:07, 19 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3oki\| PDB=3oki \| SCENE= }}~~		==Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide==
	===Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide===		<StructureSection load='3oki' size='340' side='right' caption='[[3oki]], [[Resolution\|resolution]] 2.00Å' scene=''>
	~~{{ABSTRACT_PUBMED_21134747}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3oki]] is a 4 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=3OKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OKI FirstGlance]. <br>
	==Disease==		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OKI:(2S)-2-[2-(4-CHLOROPHENYL)-1H-BENZIMIDAZOL-1-YL]-N,2-DICYCLOHEXYLETHANAMIDE'>OKI</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3okh\|3okh]], [[3olf\|3olf]], [[3omk\|3omk]], [[3omm\|3omm]], [[3oof\|3oof]], [[3ook\|3ook]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1H4, HCG_20893 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3oki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oki OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oki RCSB], [http://www.ebi.ac.uk/pdbsum/3oki PDBsum]</span></td></tr>
			</table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.		[[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.
			== 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/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Herein we describe the synthesis and structure activity relationship of a new class of FXR agonists identified from a high-throughput screening campaign. Further optimization of the original hits led to molecules that were highly active in an LDL-receptor KO model for dyslipidemia. The most promising candidate is discussed in more detail.

	~~==Function==~~		Discovery of novel and orally active FXR agonists for the potential treatment of dyslipidemia & diabetes.,Richter HG, Benson GM, Blum D, Chaput E, Feng S, Gardes C, Grether U, Hartman P, Kuhn B, Martin RE, Plancher JM, Rudolph MG, Schuler F, Taylor S, Bleicher KH Bioorg Med Chem Lett. 2011 Jan 1;21(1):191-4. Epub 2010 Nov 12. PMID:21134747<ref>PMID:21134747</ref>
	~~[[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/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, ~~such as for steroids (PGR~~, ~~GR and ER)~~, ~~retinoids (RXRs)~~, ~~thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3~~, ~~STAT5A~~, ~~STAT5B and STAT6 transcription factors~~. ~~Displays histone acetyltransferase activity toward H3 and H4~~; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. ~~Required for mediating steroid hormone response~~. ~~Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref><ref>PMID:7481822</ref><ref>~~PMID:~~9223431</ref><ref>PMID:9296499</ref><ref>PMID:9223281</ref><ref>PMID:10449719</ref>~~<ref>PMID:~~12954634~~</ref>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[3oki]] is~~ a ~~4 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=3OKI OCA].~~		</div>

	==See Also==		==See Also==
			*[[Bile acid receptor\|Bile acid receptor]]
	*[[Hormone\|Hormone]]		*[[Hormone\|Hormone]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:021134747</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Rudolph, M G.]]		[[Category: Rudolph, M G]]
	[[Category: Bile acid]]		[[Category: Bile acid]]
	[[Category: Cholesterol]]		[[Category: Cholesterol]]

OCA at 10:01, 24 March 2013

2013-03-24T10:01:12Z

← Older revision		Revision as of 10:01, 24 March 2013
Line 1:		Line 1:
	~~[[Image:3oki.png\|left\|200px]]~~

	{{STRUCTURE_3oki\| PDB=3oki \| SCENE= }}		{{STRUCTURE_3oki\| PDB=3oki \| SCENE= }}
			===Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide===
			{{ABSTRACT_PUBMED_21134747}}

	===~~Crystal structure~~ of ~~human FXR in complex with~~ (~~2S)-~~2-[2-(~~4-chlorophenyl~~)-1H-~~benzimidazol~~-~~1-yl]-N~~,2-~~dicyclohexylethanamide===~~		==Disease==
			[[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.

	~~{{ABSTRACT_PUBMED_21134747}}~~		==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/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref><ref>PMID:7481822</ref><ref>PMID:9223431</ref><ref>PMID:9296499</ref><ref>PMID:9223281</ref><ref>PMID:10449719</ref><ref>PMID:12954634</ref>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
	<ref group="xtra">PMID:021134747</ref><references group="xtra"/>		<ref group="xtra">PMID:021134747</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Rudolph, M G.]]		[[Category: Rudolph, M G.]]

OCA at 05:25, 20 October 2012

2012-10-20T05:25:16Z

← Older revision		Revision as of 05:25, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[3oki]] is a 4 chain structure ~~of [[Hormone]]~~ 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=3OKI OCA].		[[3oki]] is a 4 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=3OKI OCA].

	==See Also==		==See Also==

OCA at 09:58, 25 July 2012

2012-07-25T09:58:36Z

← Older revision		Revision as of 09:58, 25 July 2012
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	[[Image:3oki.~~jpg~~\|left\|200px]]		[[Image:3oki.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3oki", 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_3oki\| PDB=3oki \| SCENE= }}		{{STRUCTURE_3oki\| PDB=3oki \| SCENE= }}

	===Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide===		===Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_21134747}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 21134747 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_21134747}}		{{ABSTRACT_PUBMED_21134747}}

	==About this Structure==		==About this Structure==
	[[3oki]] is a 4 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=3OKI OCA].		[[3oki]] is a 4 chain structure of [[Hormone]] 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=3OKI OCA].

			==See Also==
			*[[Hormone\|Hormone]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~21134747~~</ref><references group="xtra"/>		<ref group="xtra">PMID:021134747</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Rudolph, M G.]]		[[Category: Rudolph, M G.]]

OCA: Protected "3oki" [edit=sysop:move=sysop]

2010-12-29T18:38:01Z

Protected "3oki" [edit=sysop:move=sysop]

← Older revision	Revision as of 18:38, 29 December 2010
(No difference)

OCA at 18:37, 29 December 2010

2010-12-29T18:37:57Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:3oki.jpg|left|200px]]
-The entry 3oki is ON HOLD  until Paper Publication
+<!--
-Authors: Rudolph, M.G.
+===Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide===
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 22 14:33:29 2010''
+<!--

OCA at 11:24, 22 September 2010

2010-09-22T11:24:30Z

← Older revision		Revision as of 11:24, 22 September 2010
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 3oki is ON HOLD		The entry 3oki is ON HOLD until Paper Publication

	Authors: Rudolph, M.G.		Authors: Rudolph, M.G.

	Description: ~~Discovery~~ of ~~novel~~, ~~selective and orally active FXR agonists for the potential treatment of dislipidemia and diabetes~~		Description: Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N,2-dicyclohexylethanamide

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep ~~15 10~~:36:53 2010''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 22 14:33:29 2010''