5tlt - Revision history

OCA at 14:21, 6 March 2024

OCA — Wed, 06 Mar 2024 14:21:09 GMT

←Older revision		Revision as of 14:21, 6 March 2024
Line 1:		Line 1:

	==Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with octane-1,8-diyl bis(2,3-bis(4-hydroxyphenyl)pentanoate)==		==Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with octane-1,8-diyl bis(2,3-bis(4-hydroxyphenyl)pentanoate)==
-	<StructureSection load='5tlt' size='340' side='right' caption='[[5tlt]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='5tlt' size='340' side='right'caption='[[5tlt]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tlt]] 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=5TLT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TLT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tlt]] 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=5TLT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TLT FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=7ED:8~~-{[~~2,3-BIS(4-HYDROXYPHENYL)PENTANOYL~~]~~OXY}OCTYL+(2R,3S)-2,3-BIS(4-HYDROXYPHENYL)PENTANOATE'>7ED</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.903Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">[[5tld\|5tld]], [[5tlf\|5tlf]], [[5tlg\|5tlg]], [[5tll\|5tll]], [[5tlm\|5tlm]], [[5tlo\|5tlo]], [[5tlp\|5tlp]], [[5tlu\|5tlu]], [[5tlv\|5tlv]], [[5tlx\|5tlx]], [[5tly\|5tly]], [[5tm1\|5tm1]], [[5tm2\|5tm2]], [[5tm3\|5tm3]], [[5tm4\|5tm4]], [[5tm5\|5tm5]], [[5tm6\|5tm6]], [[5tm7\|5tm7]], [[5tm8\|5tm8]], [[5tm9\|5tm9]], [[5tml\|5tml]], [[5tmm\|5tmm]], [[5tmo\|5tmo]], [[5tmq\|5tmq]], [[5tmr\|5tmr]], [[5tms\|5tms]], [[5tmt\|5tmt]], [[5tmu\|5tmu]], [[5tmv\|5tmv]], [[5tmw\|5tmw]], [[5tmz\|5tmz]], [[5tn1\|5tn1]], [[5tn3\|5tn3]], [[5tn4\|5tn4]], [[5tn5\|5tn5]], [[5tn6\|5tn6]], [[5tn7\|5tn7]], [[5tn8\|5tn8]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7ED:8-{[2,3-BIS(4-HYDROXYPHENYL)PENTANOYL]OXY}OCTYL+(2R,3S)-2,3-BIS(4-HYDROXYPHENYL)PENTANOATE'>7ED</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5tlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tlt OCA], [https://pdbe.org/5tlt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tlt RCSB], [https://www.ebi.ac.uk/pdbsum/5tlt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tlt 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=5tlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tlt OCA], [~~http~~://pdbe.org/5tlt PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5tlt RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5tlt PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5tlt 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Environmental estrogens and anti-hormone therapies for breast cancer have diverse tissue- and signaling-pathway-selective outcomes, but how estrogen receptor alpha (ERalpha) mediates this phenotypic diversity is poorly understood. We implemented a statistical approach to allow unbiased, parallel analyses of multiple crystal structures, and identified subtle perturbations of ERalpha structure by different synthetic and environmental estrogens. Many of these perturbations were in the sub-A range, within the noise of the individual structures, but contributed significantly to the activities of synthetic and environmental estrogens. Combining structural perturbation data from many structures with quantitative cellular activity profiles of the ligands enabled identification of structural rules for ligand-specific allosteric signaling-predicting activity from structure. This approach provides a framework for understanding the diverse effects of environmental estrogens and for guiding iterative medicinal chemistry efforts to generate improved breast cancer therapies, an approach that can be applied to understanding other ligand-regulated allosteric signaling pathways.	+

-	Systems Structural Biology Analysis of Ligand Effects on ERalpha Predicts Cellular Response to Environmental Estrogens and Anti-hormone Therapies.,Nwachukwu JC, Srinivasan S, Bruno NE, Nowak J, Wright NJ, Minutolo F, Rangarajan ES, Izard T, Yao XQ, Grant BJ, Kojetin DJ, Elemento O, Katzenellenbogen JA, Nettles KW Cell Chem Biol. 2016 Dec 21. pii: S2451-9456(16)30437-8. doi:, 10.1016/j.chembiol.2016.11.014. PMID:28042045<ref>PMID:28042045</ref>	+	==See Also==
-		+	*[[Estrogen receptor 3D structures\|Estrogen receptor 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 5tlt" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Bruno~~, N E~~]]	+	[[Category: Large Structures]]
-	[[Category: Elemento, O]]	+	[[Category: Bruno NE]]
-	[[Category: Katzenellenbogen~~, J A~~]]	+	[[Category: Elemento O]]
-	[[Category: Kojetin~~, D J~~]]	+	[[Category: Katzenellenbogen JA]]
-	[[Category: Nettles~~, K W~~]]	+	[[Category: Kojetin DJ]]
-	[[Category: Nowak, J]]	+	[[Category: Nettles KW]]
-	[[Category: Nwachukwu~~, J C~~]]	+	[[Category: Nowak J]]
-	[[Category: Srinivasan, S]]	+	[[Category: Nwachukwu JC]]
-	~~[[Category: Ligand binding]]~~	+	[[Category: Srinivasan S]]
-	~~[[Category: Nuclear receptor]]~~	+
-	~~[[Category: Protein-ligand complex]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription factor~~]]	+

OCA at 10:15, 22 November 2017

OCA — Wed, 22 Nov 2017 10:15:12 GMT

←Older revision		Revision as of 10:15, 22 November 2017
Line 3:		Line 3:
	<StructureSection load='5tlt' size='340' side='right' caption='[[5tlt]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='5tlt' size='340' side='right' caption='[[5tlt]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tlt]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TLT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TLT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tlt]] 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=5TLT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TLT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7ED:8-{[2,3-BIS(4-HYDROXYPHENYL)PENTANOYL]OXY}OCTYL+(2R,3S)-2,3-BIS(4-HYDROXYPHENYL)PENTANOATE'>7ED</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7ED:8-{[2,3-BIS(4-HYDROXYPHENYL)PENTANOYL]OXY}OCTYL+(2R,3S)-2,3-BIS(4-HYDROXYPHENYL)PENTANOATE'>7ED</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tld\|5tld]], [[5tlf\|5tlf]], [[5tlg\|5tlg]], [[5tll\|5tll]], [[5tlm\|5tlm]], [[5tlo\|5tlo]], [[5tlp\|5tlp]], [[5tlu\|5tlu]], [[5tlv\|5tlv]], [[5tlx\|5tlx]], [[5tly\|5tly]], [[5tm1\|5tm1]], [[5tm2\|5tm2]], [[5tm3\|5tm3]], [[5tm4\|5tm4]], [[5tm5\|5tm5]], [[5tm6\|5tm6]], [[5tm7\|5tm7]], [[5tm8\|5tm8]], [[5tm9\|5tm9]], [[5tml\|5tml]], [[5tmm\|5tmm]], [[5tmo\|5tmo]], [[5tmq\|5tmq]], [[5tmr\|5tmr]], [[5tms\|5tms]], [[5tmt\|5tmt]], [[5tmu\|5tmu]], [[5tmv\|5tmv]], [[5tmw\|5tmw]], [[5tmz\|5tmz]], [[5tn1\|5tn1]], [[5tn3\|5tn3]], [[5tn4\|5tn4]], [[5tn5\|5tn5]], [[5tn6\|5tn6]], [[5tn7\|5tn7]], [[5tn8\|5tn8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tld\|5tld]], [[5tlf\|5tlf]], [[5tlg\|5tlg]], [[5tll\|5tll]], [[5tlm\|5tlm]], [[5tlo\|5tlo]], [[5tlp\|5tlp]], [[5tlu\|5tlu]], [[5tlv\|5tlv]], [[5tlx\|5tlx]], [[5tly\|5tly]], [[5tm1\|5tm1]], [[5tm2\|5tm2]], [[5tm3\|5tm3]], [[5tm4\|5tm4]], [[5tm5\|5tm5]], [[5tm6\|5tm6]], [[5tm7\|5tm7]], [[5tm8\|5tm8]], [[5tm9\|5tm9]], [[5tml\|5tml]], [[5tmm\|5tmm]], [[5tmo\|5tmo]], [[5tmq\|5tmq]], [[5tmr\|5tmr]], [[5tms\|5tms]], [[5tmt\|5tmt]], [[5tmu\|5tmu]], [[5tmv\|5tmv]], [[5tmw\|5tmw]], [[5tmz\|5tmz]], [[5tn1\|5tn1]], [[5tn3\|5tn3]], [[5tn4\|5tn4]], [[5tn5\|5tn5]], [[5tn6\|5tn6]], [[5tn7\|5tn7]], [[5tn8\|5tn8]]</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=5tlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tlt OCA], [http://pdbe.org/5tlt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tlt RCSB], [http://www.ebi.ac.uk/pdbsum/5tlt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tlt 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=5tlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tlt OCA], [http://pdbe.org/5tlt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tlt RCSB], [http://www.ebi.ac.uk/pdbsum/5tlt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tlt ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Bruno, N E]]		[[Category: Bruno, N E]]
	[[Category: Elemento, O]]		[[Category: Elemento, O]]

OCA at 16:22, 18 January 2017

OCA — Wed, 18 Jan 2017 16:22:21 GMT

←Older revision		Revision as of 16:22, 18 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5tlt is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with octane-1,8-diyl bis(2,3-bis(4-hydroxyphenyl)pentanoate)==
		+	<StructureSection load='5tlt' size='340' side='right' caption='[[5tlt]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5tlt]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TLT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TLT FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7ED:8-{[2,3-BIS(4-HYDROXYPHENYL)PENTANOYL]OXY}OCTYL+(2R,3S)-2,3-BIS(4-HYDROXYPHENYL)PENTANOATE'>7ED</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tld\|5tld]], [[5tlf\|5tlf]], [[5tlg\|5tlg]], [[5tll\|5tll]], [[5tlm\|5tlm]], [[5tlo\|5tlo]], [[5tlp\|5tlp]], [[5tlu\|5tlu]], [[5tlv\|5tlv]], [[5tlx\|5tlx]], [[5tly\|5tly]], [[5tm1\|5tm1]], [[5tm2\|5tm2]], [[5tm3\|5tm3]], [[5tm4\|5tm4]], [[5tm5\|5tm5]], [[5tm6\|5tm6]], [[5tm7\|5tm7]], [[5tm8\|5tm8]], [[5tm9\|5tm9]], [[5tml\|5tml]], [[5tmm\|5tmm]], [[5tmo\|5tmo]], [[5tmq\|5tmq]], [[5tmr\|5tmr]], [[5tms\|5tms]], [[5tmt\|5tmt]], [[5tmu\|5tmu]], [[5tmv\|5tmv]], [[5tmw\|5tmw]], [[5tmz\|5tmz]], [[5tn1\|5tn1]], [[5tn3\|5tn3]], [[5tn4\|5tn4]], [[5tn5\|5tn5]], [[5tn6\|5tn6]], [[5tn7\|5tn7]], [[5tn8\|5tn8]]</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=5tlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tlt OCA], [http://pdbe.org/5tlt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tlt RCSB], [http://www.ebi.ac.uk/pdbsum/5tlt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tlt ProSAT]</span></td></tr>
		+	</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;">
		+	== Publication Abstract from PubMed ==
		+	Environmental estrogens and anti-hormone therapies for breast cancer have diverse tissue- and signaling-pathway-selective outcomes, but how estrogen receptor alpha (ERalpha) mediates this phenotypic diversity is poorly understood. We implemented a statistical approach to allow unbiased, parallel analyses of multiple crystal structures, and identified subtle perturbations of ERalpha structure by different synthetic and environmental estrogens. Many of these perturbations were in the sub-A range, within the noise of the individual structures, but contributed significantly to the activities of synthetic and environmental estrogens. Combining structural perturbation data from many structures with quantitative cellular activity profiles of the ligands enabled identification of structural rules for ligand-specific allosteric signaling-predicting activity from structure. This approach provides a framework for understanding the diverse effects of environmental estrogens and for guiding iterative medicinal chemistry efforts to generate improved breast cancer therapies, an approach that can be applied to understanding other ligand-regulated allosteric signaling pathways.

-	~~Authors~~:	+	Systems Structural Biology Analysis of Ligand Effects on ERalpha Predicts Cellular Response to Environmental Estrogens and Anti-hormone Therapies.,Nwachukwu JC, Srinivasan S, Bruno NE, Nowak J, Wright NJ, Minutolo F, Rangarajan ES, Izard T, Yao XQ, Grant BJ, Kojetin DJ, Elemento O, Katzenellenbogen JA, Nettles KW Cell Chem Biol. 2016 Dec 21. pii: S2451-9456(16)30437-8. doi:, 10.1016/j.chembiol.2016.11.014. PMID:28042045<ref>PMID:28042045</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5tlt" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bruno, N E]]
		+	[[Category: Elemento, O]]
		+	[[Category: Katzenellenbogen, J A]]
		+	[[Category: Kojetin, D J]]
		+	[[Category: Nettles, K W]]
		+	[[Category: Nowak, J]]
		+	[[Category: Nwachukwu, J C]]
		+	[[Category: Srinivasan, S]]
		+	[[Category: Ligand binding]]
		+	[[Category: Nuclear receptor]]
		+	[[Category: Protein-ligand complex]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription factor]]

OCA at 17:37, 9 December 2016

OCA — Fri, 09 Dec 2016 17:37:41 GMT

←Older revision		Revision as of 17:37, 9 December 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

OCA at 17:12, 26 October 2016

OCA — Wed, 26 Oct 2016 17:12:39 GMT

←Older revision		Revision as of 17:12, 26 October 2016
Line 3:		Line 3:
	The entry 5tlt is ON HOLD		The entry 5tlt is ON HOLD

-	Authors: ~~Nwachukwu, J.C., Srinivasan, S., Bruno, N.E., Nowak, J., Kojetin, D.J., Elemento, O., Katzenellenbogen, J.A., Nettles, K.W.~~	+	Authors:

-	Description: ~~Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with octane-1,8-diyl bis(2,3-bis(4-hydroxyphenyl)pentanoate)~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Nwachukwu, J.C]]
-	[[Category: Katzenellenbogen, J.A]]
-	[[Category: Bruno, N.E]]
-	[[Category: Srinivasan, S]]
-	[[Category: Kojetin, D.J]]
-	[[Category: Nowak, J]]
-	[[Category: Nettles, K.W]]
-	[[Category: Elemento, O]]

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

OCA — Wed, 19 Oct 2016 16:00:58 GMT

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

←Older revision

Revision as of 16:00, 19 October 2016

OCA: New page: '''Unreleased structure''' The entry 5tlt is ON HOLD Authors: Nwachukwu, J.C., Srinivasan, S., Bruno, N.E., Nowak, J., Kojetin, D.J., Elemento, O., Katzenellenbogen, J.A., Nettles, K.W....

OCA — Wed, 19 Oct 2016 16:00:57 GMT

New page: '''Unreleased structure''' The entry 5tlt is ON HOLD Authors: Nwachukwu, J.C., Srinivasan, S., Bruno, N.E., Nowak, J., Kojetin, D.J., Elemento, O., Katzenellenbogen, J.A., Nettles, K.W....

New page

'''Unreleased structure'''

The entry 5tlt is ON HOLD

Authors: Nwachukwu, J.C., Srinivasan, S., Bruno, N.E., Nowak, J., Kojetin, D.J., Elemento, O., Katzenellenbogen, J.A., Nettles, K.W.

Description: Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with octane-1,8-diyl bis(2,3-bis(4-hydroxyphenyl)pentanoate)
[[Category: Unreleased Structures]]
[[Category: Nwachukwu, J.C]]
[[Category: Katzenellenbogen, J.A]]
[[Category: Bruno, N.E]]
[[Category: Srinivasan, S]]
[[Category: Kojetin, D.J]]
[[Category: Nowak, J]]
[[Category: Nettles, K.W]]
[[Category: Elemento, O]]