1r5k

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[[Image:1r5k.gif|left|200px]]
[[Image:1r5k.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1r5k |SIZE=350|CAPTION= <scene name='initialview01'>1r5k</scene>, resolution 2.70&Aring;
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The line below this paragraph, containing "STRUCTURE_1r5k", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=GW5:(2E)-3-{4-[(1E)-1,2-DIPHENYLBUT-1-ENYL]PHENYL}ACRYLIC+ACID'>GW5</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE= ESR1 OR NR3A1 OR ESR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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{{STRUCTURE_1r5k| PDB=1r5k | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<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.ebi.ac.uk/pdbsum/1r5k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1r5k RCSB]</span>
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'''Human Estrogen Receptor alpha Ligand-Binding Domain In Complex With GW5638'''
'''Human Estrogen Receptor alpha Ligand-Binding Domain In Complex With GW5638'''
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[[Category: Wu, Y L.]]
[[Category: Wu, Y L.]]
[[Category: Yang, X.]]
[[Category: Yang, X.]]
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[[Category: alpha helix]]
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[[Category: Alpha helix]]
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[[Category: helical sandwich]]
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[[Category: Helical sandwich]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:06:27 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:23:33 2008''
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Revision as of 04:06, 3 May 2008

Image:1r5k.gif

Template:STRUCTURE 1r5k

Human Estrogen Receptor alpha Ligand-Binding Domain In Complex With GW5638


Overview

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.

About this Structure

1R5K is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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 Page seeded by OCA on Sat May 3 07:06:27 2008

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