1l2i
From Proteopedia
(New page: 200px<br /> <applet load="1l2i" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l2i, resolution 1.95Å" /> '''Human Estrogen Rece...) |
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| - | [[Image:1l2i.gif|left|200px]]<br /> | + | [[Image:1l2i.gif|left|200px]]<br /><applet load="1l2i" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1l2i" size=" | + | |
caption="1l2i, resolution 1.95Å" /> | caption="1l2i, resolution 1.95Å" /> | ||
'''Human Estrogen Receptor alpha Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol and a Glucocorticoid Receptor Interacting Protein 1 NR box II Peptide'''<br /> | '''Human Estrogen Receptor alpha Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol and a Glucocorticoid Receptor Interacting Protein 1 NR box II Peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The R,R enantiomer of | + | The R,R enantiomer of 5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol (THC) exerts opposite effects on the transcriptional activity of the two estrogen receptor (ER) subtypes, ER alpha and ER beta. THC acts as an ER alpha agonist and as an ER beta antagonist. We have determined the crystal structures of the ER alpha ligand binding domain (LBD) bound to both THC and a fragment of the transcriptional coactivator GRIP1, and the ER beta LBD bound to THC. THC stabilizes a conformation of the ER alpha LBD that permits coactivator association and a conformation of the ER beta LBD that prevents coactivator association. A comparison of the two structures, taken together with functional data, reveals that THC does not act on ER beta through the same mechanisms used by other known ER antagonists. Instead, THC antagonizes ER beta through a novel mechanism we term 'passive antagonism'. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1L2I is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL and ETC as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1L2I is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=ETC:'>ETC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L2I OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Agard, D | + | [[Category: Agard, D A.]] |
[[Category: Barstad, D.]] | [[Category: Barstad, D.]] | ||
| - | [[Category: Greene, G | + | [[Category: Greene, G L.]] |
| - | [[Category: Katzenellenbogen, B | + | [[Category: Katzenellenbogen, B S.]] |
| - | [[Category: Katzenellenbogen, J | + | [[Category: Katzenellenbogen, J A.]] |
| - | [[Category: Meyers, M | + | [[Category: Meyers, M J.]] |
| - | [[Category: Nettles, K | + | [[Category: Nettles, K W.]] |
| - | [[Category: Radek, J | + | [[Category: Radek, J T.]] |
| - | [[Category: Shiau, A | + | [[Category: Shiau, A K.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: ETC]] | [[Category: ETC]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:40:33 2008'' |
Revision as of 11:40, 21 February 2008
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Human Estrogen Receptor alpha Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol and a Glucocorticoid Receptor Interacting Protein 1 NR box II Peptide
Contents |
Overview
The R,R enantiomer of 5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol (THC) exerts opposite effects on the transcriptional activity of the two estrogen receptor (ER) subtypes, ER alpha and ER beta. THC acts as an ER alpha agonist and as an ER beta antagonist. We have determined the crystal structures of the ER alpha ligand binding domain (LBD) bound to both THC and a fragment of the transcriptional coactivator GRIP1, and the ER beta LBD bound to THC. THC stabilizes a conformation of the ER alpha LBD that permits coactivator association and a conformation of the ER beta LBD that prevents coactivator association. A comparison of the two structures, taken together with functional data, reveals that THC does not act on ER beta through the same mechanisms used by other known ER antagonists. Instead, THC antagonizes ER beta through a novel mechanism we term 'passive antagonism'.
Disease
Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[133430], Breast cancer OMIM:[133430], Estrogen resistance OMIM:[133430], HDL response to hormone replacement, augmented OMIM:[133430], Migraine, susceptibility to OMIM:[133430], Myocardial infarction, susceptibility to OMIM:[133430]
About this Structure
1L2I is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism., Shiau AK, Barstad D, Radek JT, Meyers MJ, Nettles KW, Katzenellenbogen BS, Katzenellenbogen JA, Agard DA, Greene GL, Nat Struct Biol. 2002 May;9(5):359-64. PMID:11953755
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