3osa - Revision history

OCA at 10:36, 21 February 2024

2024-02-21T10:36:05Z

←Older revision		Revision as of 10:36, 21 February 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>		[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Small molecules stabilize specific protein conformations from a larger ensemble, enabling molecular switches that control diverse cellular functions. We show here that the converse also holds true: the conformational state of the estrogen receptor can direct distinct orientations of the bound ligand. 'Gain-of-allostery' mutations that mimic the effects of ligand in driving protein conformation allowed crystallization of the partial agonist ligand WAY-169916 with both the canonical active and inactive conformations of the estrogen receptor. The intermediate transcriptional activity induced by WAY-169916 is associated with the ligand binding differently to the active and inactive conformations of the receptor. Analyses of a series of chemical derivatives demonstrated that altering the ensemble of ligand binding orientations changes signaling output. The coupling of different ligand binding orientations to distinct active and inactive protein conformations defines a new mechanism for titrating allosteric signaling activity.
-
-	Coupling of receptor conformation and ligand orientation determine graded activity.,Bruning JB, Parent AA, Gil G, Zhao M, Nowak J, Pace MC, Smith CL, Afonine PV, Adams PD, Katzenellenbogen JA, Nettles KW Nat Chem Biol. 2010 Nov;6(11):837-43. Epub 2010 Oct 10. PMID:20924370<ref>PMID:20924370</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3osa" style="background-color:#fffaf0;"></div>

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

OCA at 07:59, 12 July 2023

2023-07-12T07:59:59Z

←Older revision		Revision as of 07:59, 12 July 2023
Line 3:		Line 3:
	<StructureSection load='3osa' size='340' side='right'caption='[[3osa]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='3osa' size='340' side='right'caption='[[3osa]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3osa]] 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=3OSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OSA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3osa]] 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=3OSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OSA FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=KN3:4~~-[~~1-(3-METHYLBUT-~~2~~-EN-1-YL)-7-(TRIFLUOROMETHYL)-1H-INDAZOL-3-YL]BENZENE-1,3-DIOL'>KN3</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.296Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;'>~~[~~[3os8\|3os8]~~], ~~[[3os9\|3os9]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KN3:4-[1-(3-METHYLBUT-2-EN-1-YL)-7-(TRIFLUOROMETHYL)-1H-INDAZOL-3-YL]BENZENE-1,3-DIOL'>KN3</scene></td></tr>
-	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</b>~~</td><td class="sblockDat">ESR1, ESR, NR3A1 ([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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [https://pdbe.org/3osa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [https://www.ebi.ac.uk/pdbsum/3osa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3osa 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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [https://pdbe.org/3osa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [https://www.ebi.ac.uk/pdbsum/3osa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3osa ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN]] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>	+	[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Adams~~, P D~~]]	+	[[Category: Adams PD]]
-	[[Category: Afonine~~, P V~~]]	+	[[Category: Afonine PV]]
-	[[Category: Bruning, J]]	+	[[Category: Bruning J]]
-	[[Category: Gil, G]]	+	[[Category: Gil G]]
-	[[Category: Katzenellenbogen~~, J A~~]]	+	[[Category: Katzenellenbogen JA]]
-	[[Category: Nettles~~, K W~~]]	+	[[Category: Nettles KW]]
-	[[Category: Nowak, J]]	+	[[Category: Nowak J]]
-	[[Category: Pace~~, M C~~]]	+	[[Category: Pace MC]]
-	[[Category: Parent~~, A A~~]]	+	[[Category: Parent AA]]
-	[[Category: Smith~~, C L~~]]	+	[[Category: Smith CL]]
-	[[Category: Zhao, M]]	+	[[Category: Zhao M]]
-	~~[[Category: Estrogen receptor complex]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 05:45, 6 October 2021

2021-10-06T05:45:16Z

←Older revision		Revision as of 05:45, 6 October 2021
Line 1:		Line 1:

	==Estrogen Receptor==		==Estrogen Receptor==
-	<StructureSection load='3osa' size='340' side='right' caption='[[3osa]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='3osa' size='340' side='right'caption='[[3osa]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3osa]] 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=3OSA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3OSA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3osa]] 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=3OSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OSA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KN3:4-[1-(3-METHYLBUT-2-EN-1-YL)-7-(TRIFLUOROMETHYL)-1H-INDAZOL-3-YL]BENZENE-1,3-DIOL'>KN3</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KN3:4-[1-(3-METHYLBUT-2-EN-1-YL)-7-(TRIFLUOROMETHYL)-1H-INDAZOL-3-YL]BENZENE-1,3-DIOL'>KN3</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3os8\|3os8]], [[3os9\|3os9]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3os8\|3os8]], [[3os9\|3os9]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ESR1, ESR, NR3A1 ([~~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">ESR1, ESR, NR3A1 ([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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [~~http~~://pdbe.org/3osa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3osa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3osa 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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [https://pdbe.org/3osa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [https://www.ebi.ac.uk/pdbsum/3osa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3osa ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN]] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>	+	[[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN]] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[Estrogen receptor\|Estrogen receptor]]	+	*[[Estrogen receptor 3D structures\|Estrogen receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Adams, P D]]		[[Category: Adams, P D]]
	[[Category: Afonine, P V]]		[[Category: Afonine, P V]]

OCA at 11:41, 4 August 2016

2016-08-04T11:41:06Z

←Older revision		Revision as of 11:41, 4 August 2016
Line 1:		Line 1:
		+
	==Estrogen Receptor==		==Estrogen Receptor==
	<StructureSection load='3osa' size='340' side='right' caption='[[3osa]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='3osa' size='340' side='right' caption='[[3osa]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3osa]] 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=3OSA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OSA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3osa]] 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=3OSA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OSA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KN3:4-[1-(3-METHYLBUT-2-EN-1-YL)-7-(TRIFLUOROMETHYL)-1H-INDAZOL-3-YL]BENZENE-1,3-DIOL'>KN3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KN3:4-[1-(3-METHYLBUT-2-EN-1-YL)-7-(TRIFLUOROMETHYL)-1H-INDAZOL-3-YL]BENZENE-1,3-DIOL'>KN3</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3os8\|3os8]], [[3os9\|3os9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3os8\|3os8]], [[3os9\|3os9]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ESR1, ESR, NR3A1 ([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">ESR1, ESR, NR3A1 ([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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [http://www.ebi.ac.uk/pdbsum/3osa 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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [http://pdbe.org/3osa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [http://www.ebi.ac.uk/pdbsum/3osa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3osa ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 3osa" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Adams, P D]]		[[Category: Adams, P D]]
	[[Category: Afonine, P V]]		[[Category: Afonine, P V]]

OCA at 08:57, 25 December 2014

2014-12-25T08:57:01Z

←Older revision		Revision as of 08:57, 25 December 2014
Line 8:		Line 8:
	<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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [http://www.ebi.ac.uk/pdbsum/3osa 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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [http://www.ebi.ac.uk/pdbsum/3osa PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN]] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 13:26, 9 December 2014

2014-12-09T13:26:25Z

←Older revision		Revision as of 13:26, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3osa.~~png~~\|~~left~~\|~~200px~~]]	+	==Estrogen Receptor==
		+	<StructureSection load='3osa' size='340' side='right' caption='[[3osa]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3osa]] 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=3OSA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OSA FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KN3:4-[1-(3-METHYLBUT-2-EN-1-YL)-7-(TRIFLUOROMETHYL)-1H-INDAZOL-3-YL]BENZENE-1,3-DIOL'>KN3</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3os8\|3os8]], [[3os9\|3os9]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ESR1, ESR, NR3A1 ([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=3osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3osa RCSB], [http://www.ebi.ac.uk/pdbsum/3osa PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Small molecules stabilize specific protein conformations from a larger ensemble, enabling molecular switches that control diverse cellular functions. We show here that the converse also holds true: the conformational state of the estrogen receptor can direct distinct orientations of the bound ligand. 'Gain-of-allostery' mutations that mimic the effects of ligand in driving protein conformation allowed crystallization of the partial agonist ligand WAY-169916 with both the canonical active and inactive conformations of the estrogen receptor. The intermediate transcriptional activity induced by WAY-169916 is associated with the ligand binding differently to the active and inactive conformations of the receptor. Analyses of a series of chemical derivatives demonstrated that altering the ensemble of ligand binding orientations changes signaling output. The coupling of different ligand binding orientations to distinct active and inactive protein conformations defines a new mechanism for titrating allosteric signaling activity.

-	~~{{STRUCTURE_3osa\| PDB=3osa \| SCENE= }}~~	+	Coupling of receptor conformation and ligand orientation determine graded activity.,Bruning JB, Parent AA, Gil G, Zhao M, Nowak J, Pace MC, Smith CL, Afonine PV, Adams PD, Katzenellenbogen JA, Nettles KW Nat Chem Biol. 2010 Nov;6(11):837-43. Epub 2010 Oct 10. PMID:20924370<ref>PMID:20924370</ref>

-	~~===Estrogen Receptor===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20924370}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3osa]] 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=3OSA OCA].~~	+

	==See Also==		==See Also==
	*[[Estrogen receptor\|Estrogen receptor]]		*[[Estrogen receptor\|Estrogen receptor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:020924370<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Adams, P D.]]	+	[[Category: Adams, P D]]
-	[[Category: Afonine, P V.]]	+	[[Category: Afonine, P V]]
-	[[Category: Bruning, J.]]	+	[[Category: Bruning, J]]
-	[[Category: Gil, G.]]	+	[[Category: Gil, G]]
-	[[Category: Katzenellenbogen, J A.]]	+	[[Category: Katzenellenbogen, J A]]
-	[[Category: Nettles, K W.]]	+	[[Category: Nettles, K W]]
-	[[Category: Nowak, J.]]	+	[[Category: Nowak, J]]
-	[[Category: Pace, M C.]]	+	[[Category: Pace, M C]]
-	[[Category: Parent, A A.]]	+	[[Category: Parent, A A]]
-	[[Category: Smith, C L.]]	+	[[Category: Smith, C L]]
-	[[Category: Zhao, M.]]	+	[[Category: Zhao, M]]
	[[Category: Estrogen receptor complex]]		[[Category: Estrogen receptor complex]]
	[[Category: Signaling protein]]		[[Category: Signaling protein]]

OCA at 14:51, 20 October 2012

2012-10-20T14:51:28Z

←Older revision		Revision as of 14:51, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3osa]] is a 4 chain structure ~~of [[Estrogen receptor]]~~ 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=3OSA OCA].	+	[[3osa]] 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=3OSA OCA].

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

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

2012-07-26T16:31:33Z

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

←Older revision

Revision as of 16:31, 26 July 2012

OCA at 16:31, 26 July 2012

2012-07-26T16:31:31Z

←Older revision		Revision as of 16:31, 26 July 2012
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:3osa.png\|left\|200px]]
-	[[Image:3osa.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3osa", 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_3osa\| PDB=3osa \| SCENE= }}		{{STRUCTURE_3osa\| PDB=3osa \| SCENE= }}

	===Estrogen Receptor===		===Estrogen Receptor===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20924370}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20924370 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_20924370}}		{{ABSTRACT_PUBMED_20924370}}

	==About this Structure==		==About this Structure==
-	~~3OSA~~ is a 4 ~~chains~~ structure with ~~sequences~~ 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=3OSA OCA].	+	[[3osa]] is a 4 chain structure of [[Estrogen receptor]] 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=3OSA OCA].
		+
		+	==See Also==
		+	*[[Estrogen receptor\|Estrogen receptor]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20924370~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020924370</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Adams, P D.]]		[[Category: Adams, P D.]]
Line 38:		Line 29:
	[[Category: Estrogen receptor complex]]		[[Category: Estrogen receptor complex]]
	[[Category: Signaling protein]]		[[Category: Signaling protein]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 10 06:51:41 2010''

OCA at 03:40, 10 November 2010

2010-11-10T03:40:46Z

←Older revision		Revision as of 03:40, 10 November 2010
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3osa.jpg\|left\|200px]]

-	The ~~entry 3osa~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3osa", 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_3osa\| PDB=3osa \| SCENE= }}

-	~~Authors: Bruning, J., Parent, A.A., Gil, G., Zhao, M., Nowak, J., Pace, M.C., Smith, C.L., Afonine, P.V., Adams, P.D., Katzenellenbogen, J.A., Nettles, K.W.~~	+	===Estrogen Receptor===

-	Description: Estrogen Receptor

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Sep 22 14~~:34:22 2010''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_20924370}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 20924370 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_20924370}}
		+
		+	==About this Structure==
		+	3OSA is a 4 chains structure with sequences 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=3OSA OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:20924370</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Adams, P D.]]
		+	[[Category: Afonine, P V.]]
		+	[[Category: Bruning, J.]]
		+	[[Category: Gil, G.]]
		+	[[Category: Katzenellenbogen, J A.]]
		+	[[Category: Nettles, K W.]]
		+	[[Category: Nowak, J.]]
		+	[[Category: Pace, M C.]]
		+	[[Category: Parent, A A.]]
		+	[[Category: Smith, C L.]]
		+	[[Category: Zhao, M.]]
		+	[[Category: Estrogen receptor complex]]
		+	[[Category: Signaling protein]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 10 06:51:41 2010''