5u2b: Difference between revisions
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==Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with the phenylamino-substituted estrogen, (8R,9S,13S,14S,17S)-13-methyl-17-(phenylamino)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-ol, without a coactivator peptide== | ==Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with the phenylamino-substituted estrogen, (8R,9S,13S,14S,17S)-13-methyl-17-(phenylamino)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-ol, without a coactivator peptide== | ||
<StructureSection load='5u2b' size='340' side='right' caption='[[5u2b]], [[Resolution|resolution]] 2.22Å' scene=''> | <StructureSection load='5u2b' size='340' side='right'caption='[[5u2b]], [[Resolution|resolution]] 2.22Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5u2b]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U2B OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5u2b]] is a 6 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=5U2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U2B FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6WV:(8~{R},9~{S},13~{S},14~{S},17~{S})-13-METHYL-17-PHENYLAZANYL-6,7,8,9,11,12,14,15,16,17-DECAHYDROCYCLOPENTA[A]PHENANTHREN-3-OL'>6WV</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.22Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6WV:(8~{R},9~{S},13~{S},14~{S},17~{S})-13-METHYL-17-PHENYLAZANYL-6,7,8,9,11,12,14,15,16,17-DECAHYDROCYCLOPENTA[A]PHENANTHREN-3-OL'>6WV</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5u2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u2b OCA], [https://pdbe.org/5u2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u2b RCSB], [https://www.ebi.ac.uk/pdbsum/5u2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u2b 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> | ||
==See Also== | |||
*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Carlson KE]] | ||
[[Category: | [[Category: Katzenellenbogen JA]] | ||
[[Category: | [[Category: Nettles KW]] | ||
[[Category: | [[Category: Nowak J]] | ||
[[Category: | [[Category: Nwachukwu JC]] |