1r5k
From Proteopedia
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| - | [[ | + | ==Human Estrogen Receptor alpha Ligand-Binding Domain In Complex With GW5638== |
| + | <StructureSection load='1r5k' size='340' side='right' caption='[[1r5k]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1r5k]] is a 3 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=1R5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1R5K FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GW5:(2E)-3-{4-[(1E)-1,2-DIPHENYLBUT-1-ENYL]PHENYL}ACRYLIC+ACID'>GW5</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ESR1 OR NR3A1 OR ESR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1r5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r5k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1r5k RCSB], [http://www.ebi.ac.uk/pdbsum/1r5k PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == 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/r5/1r5k_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]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tamoxifen is effective for the prevention and treatment of estrogen-dependent breast cancers, but is associated with an increased incidence of endometrial tumors. We report the crystal structure of the estrogen receptor alpha (ERalpha) ligand binding domain (LBD) bound to the structurally similar compound GW5638, which has therapeutic potential and does not stimulate the uterus. Like tamoxifen, GW5638 relocates the carboxy-terminal helix (H12) to the known coactivator-docking site in the ERalpha LBD. However, GW5638 repositions residues in H12 through specific contacts with the N terminus of this helix. In contrast to tamoxifen, the resulting increase in exposed hydrophobic surface of ERalpha LBD correlates with a significant destabilization of ERalpha in MCF-7 cells. Thus, the GW5638-ERalpha LBD structure reveals an unexpected mode of SERM-mediated ER antagonism, in which the stability of ERalpha is decreased through an altered position of H12. This dual mechanism of antagonism may explain why GW5638 can inhibit tamoxifen-resistant breast tumors. | ||
| - | + | Structural basis for an unexpected mode of SERM-mediated ER antagonism.,Wu YL, Yang X, Ren Z, McDonnell DP, Norris JD, Willson TM, Greene GL Mol Cell. 2005 May 13;18(4):413-24. PMID:15893725<ref>PMID:15893725</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Estrogen receptor|Estrogen receptor]] | *[[Estrogen receptor|Estrogen receptor]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Greene, G L.]] | [[Category: Greene, G L.]] | ||
Revision as of 20:57, 28 September 2014
Human Estrogen Receptor alpha Ligand-Binding Domain In Complex With GW5638
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