3omp - Revision history

OCA at 10:35, 21 February 2024

2024-02-21T10:35:24Z

← Older revision		Revision as of 10:35, 21 February 2024
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	<StructureSection load='3omp' size='340' side='right'caption='[[3omp]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='3omp' size='340' side='right'caption='[[3omp]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3omp]] 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=3OMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OMP FirstGlance]. <br>		<table><tr><td colspan='2'>[[3omp]] 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=3OMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OMP FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=W14:2~~-~~(TRIFLUOROACETYL)-1~~,2~~,3,4-TETRAHYDROISOQUINOLIN-7-OL'>W14</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]] 2.05Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;'>[[3ols\|3ols]]~~, ~~[[3olm\|3olm]]~~, ~~[[3omo\|3omo]]~~, ~~[[3omq\|3omq]]</div></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W14:2-(TRIFLUOROACETYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-OL'>W14</scene></td></tr>
	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</b>~~</td><td class="sblockDat">ESR2, ESTRB, NR3A2 ([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=3omp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3omp OCA], [https://pdbe.org/3omp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3omp RCSB], [https://www.ebi.ac.uk/pdbsum/3omp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3omp 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=3omp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3omp OCA], [https://pdbe.org/3omp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3omp RCSB], [https://www.ebi.ac.uk/pdbsum/3omp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3omp 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/ESR2_HUMAN ESR2_HUMAN]] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual. [[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/ESR2_HUMAN ESR2_HUMAN] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	A library of small tetrahydroisoquinoline ligands, previously identified via structure- and chemistry-based hierarchical organization of library scaffolds in tree-like arrangements, has been generated as novel estrogen receptor agonistic fragments via traditional medicinal chemistry exploration. The approach described has allowed for the rapid evaluation of a structure-activity relationship of the ligands concerning estrogen receptor affinity and estrogen receptor beta subtype selectivity. The structural biological insights obtained from the fragments aid the understanding of larger analogues and constitute attractive starting points for further optimization.

	Design and Evaluation of Fragment-Like Estrogen Receptor Tetrahydroisoquinoline Ligands from a Scaffold-Detection Approach.,Mocklinghoff S, van Otterlo WA, Rose R, Fuchs S, Zimmermann TJ, Dominguez Seoane M, Waldmann H, Ottmann C, Brunsveld L J Med Chem. 2011 Mar 7. PMID:21381753<ref>PMID:21381753</ref>

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

	==See Also==		==See Also==
	*[[Estrogen receptor 3D structures\|Estrogen receptor 3D structures]]		*[[Estrogen receptor 3D structures\|Estrogen receptor 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Brunsveld, L]]		[[Category: Brunsveld L]]
	[[Category: ~~Fuchs, S~~]]		[[Category: Dominguez Seoane M]]
	[[Category: ~~Moecklinghoff,~~ S]]		[[Category: Fuchs S]]
	[[Category: ~~Otterlo, W A.van~~]]		[[Category: Moecklinghoff S]]
	[[Category: Ottmann, C]]		[[Category: Ottmann C]]
	[[Category: Rose, R]]		[[Category: Rose R]]
	~~[[Category: Seoane, M Dominguez~~]]		[[Category: Waldmann H]]
	[[Category: Waldmann, H]]		[[Category: Van Otterlo WA]]
	[[Category: ~~Protein binding]]~~
	~~[[Category: Steroid binding~~]]

OCA at 10:49, 18 May 2022

2022-05-18T10:49:17Z

← Older revision		Revision as of 10:49, 18 May 2022
Line 1:		Line 1:

	==Fragment-Based Design of novel Estrogen Receptor Ligands==		==Fragment-Based Design of novel Estrogen Receptor Ligands==
	<StructureSection load='3omp' size='340' side='right' caption='[[3omp]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='3omp' size='340' side='right'caption='[[3omp]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3omp]] 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=3OMP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3OMP FirstGlance]. <br>		<table><tr><td colspan='2'>[[3omp]] 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=3OMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OMP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=W14:2-(TRIFLUOROACETYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-OL'>W14</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W14:2-(TRIFLUOROACETYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-OL'>W14</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ols\|3ols]], [[3olm\|3olm]], [[3omo\|3omo]], [[3omq\|3omq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ols\|3ols]], [[3olm\|3olm]], [[3omo\|3omo]], [[3omq\|3omq]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ESR2, ESTRB, NR3A2 ([~~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">ESR2, ESTRB, NR3A2 ([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=3omp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3omp OCA], [~~http~~://pdbe.org/3omp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3omp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3omp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3omp 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=3omp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3omp OCA], [https://pdbe.org/3omp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3omp RCSB], [https://www.ebi.ac.uk/pdbsum/3omp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3omp 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/ESR2_HUMAN ESR2_HUMAN]] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual. [[~~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/ESR2_HUMAN ESR2_HUMAN]] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual. [[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 ==
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	==See Also==		==See Also==
	*[[Estrogen receptor\|Estrogen receptor]]		*[[Estrogen receptor 3D structures\|Estrogen receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 30:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Brunsveld, L]]		[[Category: Brunsveld, L]]
	[[Category: Fuchs, S]]		[[Category: Fuchs, S]]

OCA at 23:24, 5 August 2016

2016-08-05T23:24:06Z

← Older revision		Revision as of 23:24, 5 August 2016
Line 1:		Line 1:

	==Fragment-Based Design of novel Estrogen Receptor Ligands==		==Fragment-Based Design of novel Estrogen Receptor Ligands==
	<StructureSection load='3omp' size='340' side='right' caption='[[3omp]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='3omp' size='340' side='right' caption='[[3omp]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3omp]] 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=3OMP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OMP FirstGlance]. <br>		<table><tr><td colspan='2'>[[3omp]] 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=3OMP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OMP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=W14:2-(TRIFLUOROACETYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-OL'>W14</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=W14:2-(TRIFLUOROACETYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-OL'>W14</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ols\|3ols]], [[3olm\|3olm]], [[3omo\|3omo]], [[3omq\|3omq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ols\|3ols]], [[3olm\|3olm]], [[3omo\|3omo]], [[3omq\|3omq]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ESR2, ESTRB, NR3A2 ([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">ESR2, ESTRB, NR3A2 ([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=3omp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3omp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3omp RCSB], [http://www.ebi.ac.uk/pdbsum/3omp 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=3omp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3omp OCA], [http://pdbe.org/3omp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3omp RCSB], [http://www.ebi.ac.uk/pdbsum/3omp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3omp 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 3omp" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Brunsveld, L]]		[[Category: Brunsveld, L]]
	[[Category: Fuchs, S]]		[[Category: Fuchs, S]]

OCA at 07:21, 19 December 2014

2014-12-19T07:21:10Z

← Older revision		Revision as of 07:21, 19 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3omp\| PDB=3omp \| SCENE= }}~~		==Fragment-Based Design of novel Estrogen Receptor Ligands==
	===Fragment-Based Design of novel Estrogen Receptor Ligands===		<StructureSection load='3omp' size='340' side='right' caption='[[3omp]], [[Resolution\|resolution]] 2.05Å' scene=''>
	~~{{ABSTRACT_PUBMED_21381753}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3omp]] 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=3OMP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OMP FirstGlance]. <br>
	==Disease==		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=W14:2-(TRIFLUOROACETYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-OL'>W14</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ols\|3ols]], [[3olm\|3olm]], [[3omo\|3omo]], [[3omq\|3omq]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ESR2, ESTRB, NR3A2 ([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=3omp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3omp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3omp RCSB], [http://www.ebi.ac.uk/pdbsum/3omp 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/ESR2_HUMAN ESR2_HUMAN]] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual. [[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 ==
			A library of small tetrahydroisoquinoline ligands, previously identified via structure- and chemistry-based hierarchical organization of library scaffolds in tree-like arrangements, has been generated as novel estrogen receptor agonistic fragments via traditional medicinal chemistry exploration. The approach described has allowed for the rapid evaluation of a structure-activity relationship of the ligands concerning estrogen receptor affinity and estrogen receptor beta subtype selectivity. The structural biological insights obtained from the fragments aid the understanding of larger analogues and constitute attractive starting points for further optimization.

	~~==Function==~~		Design and Evaluation of Fragment-Like Estrogen Receptor Tetrahydroisoquinoline Ligands from a Scaffold-Detection Approach.,Mocklinghoff S, van Otterlo WA, Rose R, Fuchs S, Zimmermann TJ, Dominguez Seoane M, Waldmann H, Ottmann C, Brunsveld L J Med Chem. 2011 Mar 7. PMID:21381753<ref>PMID:21381753</ref>
	[[http://www.uniprot.org/uniprot/ESR2_HUMAN ESR2_HUMAN]] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ~~ESR2 is rapidly lost at 37 degrees Celsius in the absence~~ of ~~ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA~~-binding at elevated temperature is more gradual. [[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>
	~~[[3omp]] 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=3OMP OCA].~~		</div>

	==See Also==		==See Also==
	*[[Estrogen receptor\|Estrogen receptor]]		*[[Estrogen receptor\|Estrogen receptor]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:021381753</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Brunsveld, L.]]		[[Category: Brunsveld, L]]
	[[Category: Fuchs, S.]]		[[Category: Fuchs, S]]
	[[Category: Moecklinghoff, S.]]		[[Category: Moecklinghoff, S]]
	[[Category: Otterlo, W A.van.]]		[[Category: Otterlo, W A.van]]
	[[Category: Ottmann, C.]]		[[Category: Ottmann, C]]
	[[Category: Rose, R.]]		[[Category: Rose, R]]
	[[Category: Seoane, M Dominguez.]]		[[Category: Seoane, M Dominguez]]
	[[Category: Waldmann, H.]]		[[Category: Waldmann, H]]
	[[Category: Protein binding]]		[[Category: Protein binding]]
	[[Category: Steroid binding]]		[[Category: Steroid binding]]

OCA at 07:17, 25 March 2013

2013-03-25T07:17:36Z

← Older revision		Revision as of 07:17, 25 March 2013
Line 1:		Line 1:
	~~[[Image:3omp.png\|left\|200px]]~~

	{{STRUCTURE_3omp\| PDB=3omp \| SCENE= }}		{{STRUCTURE_3omp\| PDB=3omp \| SCENE= }}
			===Fragment-Based Design of novel Estrogen Receptor Ligands===
			{{ABSTRACT_PUBMED_21381753}}

	===~~Fragment~~-~~Based Design~~ of ~~novel Estrogen Receptor Ligands===~~		==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_21381753}}~~		==Function==
			[[http://www.uniprot.org/uniprot/ESR2_HUMAN ESR2_HUMAN]] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual. [[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:021381753</ref><references group="xtra"/>		<ref group="xtra">PMID:021381753</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Brunsveld, L.]]		[[Category: Brunsveld, L.]]

OCA at 13:48, 20 October 2012

2012-10-20T13:48:42Z

← Older revision		Revision as of 13:48, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[3omp]] 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=3OMP OCA].		[[3omp]] 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=3OMP OCA].

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

OCA at 13:10, 26 July 2012

2012-07-26T13:10:58Z

← Older revision		Revision as of 13:10, 26 July 2012
Line 1:		Line 1:
	[[Image:3omp.png\|left\|200px]]		[[Image:3omp.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3omp", 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_3omp\| PDB=3omp \| SCENE= }}		{{STRUCTURE_3omp\| PDB=3omp \| SCENE= }}

	===Fragment-Based Design of novel Estrogen Receptor Ligands===		===Fragment-Based Design of novel Estrogen Receptor Ligands===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_21381753}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 21381753 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_21381753}}		{{ABSTRACT_PUBMED_21381753}}

	==About this Structure==		==About this Structure==
	[[3omp]] 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=3OMP OCA].		[[3omp]] 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=3OMP OCA].

			==See Also==
			*[[Estrogen receptor\|Estrogen receptor]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~21381753~~</ref><references group="xtra"/>		<ref group="xtra">PMID:021381753</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Brunsveld, L.]]		[[Category: Brunsveld, L.]]
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	[[Category: Seoane, M Dominguez.]]		[[Category: Seoane, M Dominguez.]]
	[[Category: Waldmann, H.]]		[[Category: Waldmann, H.]]
			[[Category: Protein binding]]
			[[Category: Steroid binding]]

OCA at 09:57, 21 April 2011

2011-04-21T09:57:50Z

← Older revision		Revision as of 09:57, 21 April 2011
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	[[Image:3omp.~~jpg~~\|left\|200px]]		[[Image:3omp.png\|left\|200px]]

	<!--		<!--

OCA at 08:23, 16 March 2011

2011-03-16T08:23:09Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:3omp.jpg|left|200px]]
-The entry 3omp is ON HOLD  until Paper Publication
+<!--
-Authors: Moecklinghoff, S., van Otterlo, W.A., Rose, R., Fuchs, S., Dominguez Seoane, M., Waldmann, H., Ottmann, C., Brunsveld, L.
+===Fragment-Based Design of novel Estrogen Receptor Ligands===
-Description: Fragment-Based Design of novel Estrogen Receptor Ligands

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

2011-01-19T05:46:40Z

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

← Older revision	Revision as of 05:46, 19 January 2011
(No difference)