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| - | | + | #REDIRECT [[7ujf]] This PDB entry is obsolete and replaced by 7ujf |
| - | ==Estrogen Receptor Alpha Ligand Binding Domain in Complex with a Methylated Lasofoxifene Derivative with Selective Estrogen Receptor Degrader Properties==
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| - | <StructureSection load='6vmu' size='340' side='right'caption='[[6vmu]], [[Resolution|resolution]] 1.70Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[6vmu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VMU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6VMU FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=R3V:(5R,6S)-5-(4-{2-[(3S)-3-methylpyrrolidin-1-yl]ethoxy}phenyl)-6-phenyl-5,6,7,8-tetrahydronaphthalen-2-ol'>R3V</scene></td></tr>
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| - | <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=6vmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vmu OCA], [http://pdbe.org/6vmu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vmu RCSB], [http://www.ebi.ac.uk/pdbsum/6vmu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vmu ProSAT]</span></td></tr>
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| - | </table>
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| - | == Function ==
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| - | [[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>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Large Structures]]
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| - | [[Category: Fanning, S W]]
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| - | [[Category: Greene, G L]]
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| - | [[Category: Breast cancer]]
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| - | [[Category: Estrogen receptor]]
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| - | [[Category: Nuclear hormone receptor]]
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| - | [[Category: Selective estrogen receptor degrader]]
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| - | [[Category: Serd]]
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| - | [[Category: Transcription]]
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