5ak2
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Oxyphenylpropenoic acids as Oral Selective Estrogen Receptor Down- Regulators.== | |
| + | <StructureSection load='5ak2' size='340' side='right'caption='[[5ak2]], [[Resolution|resolution]] 2.19Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5ak2]] is a 2 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=5AK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AK2 FirstGlance]. <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]] 2.19Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=85Z:(E)-3-[4-[[3-(4-FLUORANYL-2-METHYL-PHENYL)-7-OXIDANYL-2-OXIDANYLIDENE-CHROMEN-4-YL]METHYL]PHENYL]PROP-2-ENOIC+ACID'>85Z</scene></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=5ak2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ak2 OCA], [https://pdbe.org/5ak2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ak2 RCSB], [https://www.ebi.ac.uk/pdbsum/5ak2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ak2 ProSAT]</span></td></tr> | ||
| + | </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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A novel estrogen receptor down-regulator, 7-hydroxycoumarin (5, SS5020), has been reported with antitumor effects against chemically induced mammary tumors. Here, we report on our own investigation of 7-hydroxycoumarins as potential selective estrogen receptor down-regulators, which led us to the discovery of potent down-regulating antagonists, such as 33. Subsequent optimization and removal of the 7-hydroxy group led to coumarin 59, which had increased potency and improved rat bioavailability relative to SS5020. | ||
| - | + | Investigation of (E)-3-[4-(2-Oxo-3-aryl-chromen-4-yl)oxyphenyl]acrylic Acids as Oral Selective Estrogen Receptor Down-Regulators.,Degorce SL, Bailey A, Callis R, De Savi C, Ducray R, Lamont G, MacFaul P, Maudet M, Martin S, Morgentin R, Norman RA, Peru A, Pink JH, Ple PA, Roberts B, Scott JS J Med Chem. 2015 Apr 1. PMID:25790336<ref>PMID:25790336</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5ak2" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: De Savi | + | *[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: Lamot | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Bailey A]] |
| + | [[Category: Callis R]] | ||
| + | [[Category: De Savi C]] | ||
| + | [[Category: Degorce S]] | ||
| + | [[Category: Ducray R]] | ||
| + | [[Category: Lamot P]] | ||
| + | [[Category: MacFaul P]] | ||
| + | [[Category: Maudet M]] | ||
| + | [[Category: Norman RA]] | ||
| + | [[Category: Phillips C]] | ||
| + | [[Category: Scott JS]] | ||
Current revision
Oxyphenylpropenoic acids as Oral Selective Estrogen Receptor Down- Regulators.
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Categories: Homo sapiens | Large Structures | Bailey A | Callis R | De Savi C | Degorce S | Ducray R | Lamot P | MacFaul P | Maudet M | Norman RA | Phillips C | Scott JS
