4s0t - Revision history

OCA at 12:57, 1 March 2024

2024-03-01T12:57:41Z

←Older revision		Revision as of 12:57, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4s0t]] 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=4S0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S0T FirstGlance]. <br>		<table><tr><td colspan='2'>[[4s0t]] 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=4S0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S0T FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</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]] 3.14Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [https://pdbe.org/4s0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [https://www.ebi.ac.uk/pdbsum/4s0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0t 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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [https://pdbe.org/4s0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [https://www.ebi.ac.uk/pdbsum/4s0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0t ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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>		[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 ==
-	The human pregnane X receptor (PXR) is a promiscuous nuclear receptor that functions as a sensor to a wide variety of xenobiotics and regulates expression of several drug metabolizing enzymes and transporters. We have generated "Adnectins", derived from 10th fibronectin type III domain (10Fn3), that target the PXR ligand binding domain (LBD) interactions with the steroid receptor co-activator-1 (SRC-1) peptide, displacing SRC-1 binding. Adnectins are structurally homologous to the immunoglobulin superfamily. Three different co-crystal structures of PXR LBD with Adnectin-1 and CCR1 (CC chemokine receptor-1) antagonist Compound-1 were determined. This structural information was used to modulate PXR affinity for a related CCR1 antagonist compound that entered into clinical trials for rheumatoid arthritis. The structures of PXR with Adnectin-1 reveal specificity of Adnectin-1 in not only targeting the interface of the SRC-1 interactions but also engaging the same set of residues that are involved in binding of SRC-1 to PXR. Substituting SRC-1 with Adnectin-1 does not alter the binding conformation of Compound-1 in the ligand binding pocket. The structure also reveals the possibility of using Adnectins as crystallization chaperones to generate structures of PXR with compounds of interest.
-
-	Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR.,Khan JA, Camac DM, Low S, Tebben AJ, Wensel DL, Wright MC, Su J, Jenny V, Gupta RD, Ruzanov M, Russo KA, Bell A, An Y, Bryson JW, Gao M, Gambhire P, Baldwin ET, Gardner D, Cavallaro CL, Duncia JV, Hynes J Jr J Mol Biol. 2015 Jan 8. pii: S0022-2836(15)00002-9. doi:, 10.1016/j.jmb.2014.12.022. PMID:25579995<ref>PMID:25579995</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4s0t" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
-	*[[Pregnane X receptor\|Pregnane X receptor]]	+	*[[Pregnane X receptor 3D structures\|Pregnane X receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:38, 15 March 2023

2023-03-15T10:38:05Z

←Older revision		Revision as of 10:38, 15 March 2023
Line 1:		Line 1:

	==STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND WITH ADNECTIN-1 AND COMPOUND-1==		==STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND WITH ADNECTIN-1 AND COMPOUND-1==
-	<StructureSection load='4s0t' size='340' side='right' caption='[[4s0t]], [[Resolution\|resolution]] 3.14Å' scene=''>	+	<StructureSection load='4s0t' size='340' side='right'caption='[[4s0t]], [[Resolution\|resolution]] 3.14Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4s0t]] 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=4S0T OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4S0T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4s0t]] 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=4S0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S0T FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4xhd\|4xhd]], [[4s0s\|4s0s]]</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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [https://pdbe.org/4s0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [https://www.ebi.ac.uk/pdbsum/4s0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0t ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1I2, PXR ([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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [~~http~~://pdbe.org/4s0t PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4s0t PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0t ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4s0t" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4s0t" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Pregnane X receptor\|Pregnane X receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Camac, D M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Khan, J A~~]]	+	[[Category: Camac DM]]
-	[[Category: ~~Multiple binding mode]]~~	+	[[Category: Khan JA]]
-	~~[[Category: Nuclear hormone receptor]]~~	+
-	~~[[Category: Nuclear receptor]]~~	+
-	~~[[Category: Promiscuous]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Xenobiotic~~]]	+

OCA at 07:21, 29 November 2017

2017-11-29T07:21:11Z

←Older revision		Revision as of 07:21, 29 November 2017
Line 3:		Line 3:
	<StructureSection load='4s0t' size='340' side='right' caption='[[4s0t]], [[Resolution\|resolution]] 3.14Å' scene=''>		<StructureSection load='4s0t' size='340' side='right' caption='[[4s0t]], [[Resolution\|resolution]] 3.14Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4s0t]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S0T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S0T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4s0t]] 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=4S0T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S0T FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4xhd\|4xhd]], [[~~4sos~~\|~~4sos~~]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4xhd\|4xhd]], [[4s0s\|4s0s]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1I2, PXR ([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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [http://pdbe.org/4s0t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [http://www.ebi.ac.uk/pdbsum/4s0t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0t 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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [http://pdbe.org/4s0t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [http://www.ebi.ac.uk/pdbsum/4s0t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0t ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Camac, D M]]		[[Category: Camac, D M]]
	[[Category: Khan, J A]]		[[Category: Khan, J A]]

OCA at 01:23, 19 January 2017

2017-01-19T01:23:35Z

←Older revision		Revision as of 01:23, 19 January 2017
Line 1:		Line 1:
		+
	==STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND WITH ADNECTIN-1 AND COMPOUND-1==		==STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND WITH ADNECTIN-1 AND COMPOUND-1==
	<StructureSection load='4s0t' size='340' side='right' caption='[[4s0t]], [[Resolution\|resolution]] 3.14Å' scene=''>		<StructureSection load='4s0t' size='340' side='right' caption='[[4s0t]], [[Resolution\|resolution]] 3.14Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4xhd\|4xhd]], [[4sos\|4sos]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4xhd\|4xhd]], [[4sos\|4sos]]</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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [http://www.ebi.ac.uk/pdbsum/4s0t 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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [http://pdbe.org/4s0t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [http://www.ebi.ac.uk/pdbsum/4s0t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0t ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4s0t" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:50, 7 February 2015

2015-02-07T15:50:03Z

←Older revision		Revision as of 15:50, 7 February 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND WITH ADNECTIN-1 AND COMPOUND-1==
		+	<StructureSection load='4s0t' size='340' side='right' caption='[[4s0t]], [[Resolution\|resolution]] 3.14Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4s0t]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S0T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S0T FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4xhd\|4xhd]], [[4sos\|4sos]]</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=4s0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4s0t RCSB], [http://www.ebi.ac.uk/pdbsum/4s0t PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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 ==
		+	The human pregnane X receptor (PXR) is a promiscuous nuclear receptor that functions as a sensor to a wide variety of xenobiotics and regulates expression of several drug metabolizing enzymes and transporters. We have generated "Adnectins", derived from 10th fibronectin type III domain (10Fn3), that target the PXR ligand binding domain (LBD) interactions with the steroid receptor co-activator-1 (SRC-1) peptide, displacing SRC-1 binding. Adnectins are structurally homologous to the immunoglobulin superfamily. Three different co-crystal structures of PXR LBD with Adnectin-1 and CCR1 (CC chemokine receptor-1) antagonist Compound-1 were determined. This structural information was used to modulate PXR affinity for a related CCR1 antagonist compound that entered into clinical trials for rheumatoid arthritis. The structures of PXR with Adnectin-1 reveal specificity of Adnectin-1 in not only targeting the interface of the SRC-1 interactions but also engaging the same set of residues that are involved in binding of SRC-1 to PXR. Substituting SRC-1 with Adnectin-1 does not alter the binding conformation of Compound-1 in the ligand binding pocket. The structure also reveals the possibility of using Adnectins as crystallization chaperones to generate structures of PXR with compounds of interest.

-	~~The entry 4s0t is ON HOLD~~	+	Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR.,Khan JA, Camac DM, Low S, Tebben AJ, Wensel DL, Wright MC, Su J, Jenny V, Gupta RD, Ruzanov M, Russo KA, Bell A, An Y, Bryson JW, Gao M, Gambhire P, Baldwin ET, Gardner D, Cavallaro CL, Duncia JV, Hynes J Jr J Mol Biol. 2015 Jan 8. pii: S0022-2836(15)00002-9. doi:, 10.1016/j.jmb.2014.12.022. PMID:25579995<ref>PMID:25579995</ref>

-	~~Authors: Khan~~, J.A., Camac, D.M.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND TETHERED WITH ADNECTIN-1 AND COMPOUND-1~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: ~~Camac, D.M~~]]	+	__TOC__
-	[[Category: ~~Khan, J.A~~]]	+	</StructureSection>
		+	[[Category: Camac, D M]]
		+	[[Category: Khan, J A]]
		+	[[Category: Multiple binding mode]]
		+	[[Category: Nuclear hormone receptor]]
		+	[[Category: Nuclear receptor]]
		+	[[Category: Promiscuous]]
		+	[[Category: Transcription]]
		+	[[Category: Xenobiotic]]

OCA: Protected "4s0t" [edit=sysop:move=sysop]

2015-01-14T10:58:35Z

Protected "4s0t" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:58, 14 January 2015

OCA: New page: '''Unreleased structure''' The entry 4s0t is ON HOLD Authors: Khan, J.A., Camac, D.M. Description: STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND TETHERED WITH ADNE...

2015-01-14T10:58:34Z

New page: '''Unreleased structure''' The entry 4s0t is ON HOLD Authors: Khan, J.A., Camac, D.M. Description: STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND TETHERED WITH ADNE...

New page

'''Unreleased structure'''

The entry 4s0t is ON HOLD

Authors: Khan, J.A., Camac, D.M.

Description: STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND TETHERED WITH ADNECTIN-1 AND COMPOUND-1
[[Category: Unreleased Structures]]
[[Category: Camac, D.M]]
[[Category: Khan, J.A]]