2ayr: Difference between revisions

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==A SERM Designed for the Treatment of Uterine Leiomyoma with Unique Tissue Specificity for Uterus and Ovaries in Rats==

== Structural highlights ==

<table><tr><td colspan='2'>[[2ayr]] is a 1 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=2AYR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2AYR FirstGlance]. <br>

<table><tr><td colspan='2'>[[2ayr]] is a 1 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=2AYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AYR FirstGlance]. <br>

</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L4G:6-(4-METHYLSULFONYL-PHENYL)-5-[4-(2-PIPERIDIN-1-YLETHOXY)PHENOXY]NAPHTHALEN-2-OL'>L4G</scene>~~<br>~~

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr>

~~<tr><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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L4G:6-(4-METHYLSULFONYL-PHENYL)-5-[4-(2-PIPERIDIN-1-YLETHOXY)PHENOXY]NAPHTHALEN-2-OL'>L4G</scene></td></tr>

<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2ayr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ayr OCA], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2ayr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2ayr PDBsum]</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=2ayr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ayr OCA], [https://pdbe.org/2ayr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ayr RCSB], [https://www.ebi.ac.uk/pdbsum/2ayr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ayr ProSAT]</span></td></tr>

<table>

</table>

== 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>

== Evolutionary Conservation ==

[[Image:Consurf_key_small.gif|200px|right]]

Check<jmol>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ay/2ayr_consurf.spt"</scriptWhenChecked>

<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ay/2ayr_consurf.spt"</scriptWhenChecked>

<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>

<text>to colour the structure by Evolutionary Conservation</text>

</jmolCheckbox>

</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].

</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ayr ConSurf].

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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

==See Also==

*[[Estrogen receptor|Estrogen receptor]]

*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]

== References ==

Line 33:

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</StructureSection>

[[Category: Homo sapiens]]

[[Category: Bryant~~, H U.~~]]

[[Category: Large Structures]]

[[Category: Cohen~~, I R.~~]]

[[Category: Bryant HU]]

[[Category: Dally~~, R D.~~]]

[[Category: Cohen IR]]

[[Category: Dodge~~, J A.~~]]

[[Category: Dally RD]]

[[Category: Fong~~, K C.~~]]

[[Category: Dodge JA]]

[[Category: Frank~~, S A.~~]]

[[Category: Fong KC]]

[[Category: Geiser~~, A G.~~]]

[[Category: Frank SA]]

[[Category: Hinklin, R.]]

[[Category: Geiser AG]]

[[Category: Hummel~~, C W.~~]]

[[Category: Hinklin R]]

[[Category: Jones~~, S A.~~]]

[[Category: Hummel CW]]

[[Category: Lewis, G.]]

[[Category: Jones SA]]

[[Category: McCann~~, D J.~~]]

[[Category: Lewis G]]

[[Category: Rudman~~, D G.~~]]

[[Category: McCann DJ]]

[[Category: Shepherd~~, T A.~~]]

[[Category: Rudman DG]]

[[Category: Tian, H.]]

[[Category: Shepherd TA]]

[[Category: Wallace~~, O B.~~]]

[[Category: Tian H]]

[[Category: Wang, Y~~.]]~~

[[Category: Wallace OB]]

~~[[Category: Ligand-binding]]~~

[[Category: Wang Y]]

~~[[Category: Receptor]]~~

~~[[Category: Serm]]~~

~~[[Category: Transcription]]~~

~~[[Category: Transcription regulation~~]]

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@@ Line 1: / Line 1: @@
 ==A SERM Designed for the Treatment of Uterine Leiomyoma with Unique Tissue Specificity for Uterus and Ovaries in Rats==
-<StructureSection load='2ayr' size='340' side='right' caption='[[2ayr]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='2ayr' size='340' side='right'caption='[[2ayr]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ayr]] is a 1 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=2AYR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AYR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ayr]] is a 1 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=2AYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AYR FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L4G:6-(4-METHYLSULFONYL-PHENYL)-5-[4-(2-PIPERIDIN-1-YLETHOXY)PHENOXY]NAPHTHALEN-2-OL'>L4G</scene><br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-<tr><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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L4G:6-(4-METHYLSULFONYL-PHENYL)-5-[4-(2-PIPERIDIN-1-YLETHOXY)PHENOXY]NAPHTHALEN-2-OL'>L4G</scene></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ayr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ayr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ayr RCSB], [http://www.ebi.ac.uk/pdbsum/2ayr PDBsum]</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=2ayr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ayr OCA], [https://pdbe.org/2ayr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ayr RCSB], [https://www.ebi.ac.uk/pdbsum/2ayr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ayr ProSAT]</span></td></tr>
-<table>
+</table>
+== 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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
    <jmolCheckbox>
-     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ay/2ayr_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ay/2ayr_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
    </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ayr ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2ayr" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Estrogen receptor|Estrogen receptor]]
+*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]
 == References ==
 <references/>
@@ Line 33: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bryant, H U.]]
+[[Category: Large Structures]]
-[[Category: Cohen, I R.]]
+[[Category: Bryant HU]]
-[[Category: Dally, R D.]]
+[[Category: Cohen IR]]
-[[Category: Dodge, J A.]]
+[[Category: Dally RD]]
-[[Category: Fong, K C.]]
+[[Category: Dodge JA]]
-[[Category: Frank, S A.]]
+[[Category: Fong KC]]
-[[Category: Geiser, A G.]]
+[[Category: Frank SA]]
-[[Category: Hinklin, R.]]
+[[Category: Geiser AG]]
-[[Category: Hummel, C W.]]
+[[Category: Hinklin R]]
-[[Category: Jones, S A.]]
+[[Category: Hummel CW]]
-[[Category: Lewis, G.]]
+[[Category: Jones SA]]
-[[Category: McCann, D J.]]
+[[Category: Lewis G]]
-[[Category: Rudman, D G.]]
+[[Category: McCann DJ]]
-[[Category: Shepherd, T A.]]
+[[Category: Rudman DG]]
-[[Category: Tian, H.]]
+[[Category: Shepherd TA]]
-[[Category: Wallace, O B.]]
+[[Category: Tian H]]
-[[Category: Wang, Y.]]
+[[Category: Wallace OB]]
-[[Category: Ligand-binding]]
+[[Category: Wang Y]]
-[[Category: Receptor]]
-[[Category: Serm]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]