1l2i
From Proteopedia
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|PDB= 1l2i |SIZE=350|CAPTION= <scene name='initialview01'>1l2i</scene>, resolution 1.95Å | |PDB= 1l2i |SIZE=350|CAPTION= <scene name='initialview01'>1l2i</scene>, resolution 1.95Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> | + | |LIGAND= <scene name='pdbligand=CCS:CARBOXYMETHYLATED+CYSTEINE'>CCS</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ETC:(R,R)-5,11-CIS-DIETHYL-5,6,11,12-TETRAHYDROCHRYSENE-2,8-DIOL'>ETC</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[3erd|3ERD]], [[1l2j|1L2J]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l2i OCA], [http://www.ebi.ac.uk/pdbsum/1l2i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1l2i RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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'. | 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'. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Estrogen resistance OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], HDL response to hormone replacement, augmented OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Migraine, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Radek, J T.]] | [[Category: Radek, J T.]] | ||
[[Category: Shiau, A K.]] | [[Category: Shiau, A K.]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: ETC]] | ||
[[Category: agonist]] | [[Category: agonist]] | ||
[[Category: coactivator]] | [[Category: coactivator]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:57:05 2008'' |
Revision as of 18:57, 30 March 2008
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| , resolution 1.95Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Related: | 3ERD, 1L2J
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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'.
About this Structure
1L2I is a Protein complex structure of sequences from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 21:57:05 2008
