1l2j: Difference between revisions

Revision as of 14:40, 21 February 2008

Human Estrogen Receptor beta Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol

OverviewOverview

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 StructureAbout this Structure

1L2J is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

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 Thu Feb 21 13:40:34 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:1l2j.gif|left|200px]]<br />
+[[Image:1l2j.gif|left|200px]]<br /><applet load="1l2j" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1l2j" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1l2j, resolution 2.95&Aring;" />
 '''Human Estrogen Receptor beta Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol'''<br />
 ==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'.
 ==About this Structure==
-L2J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ETC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1L2J OCA].
+L2J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ETC:'>ETC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L2J OCA].
 ==Reference==
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 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Agard, D.A.]]
+[[Category: Agard, D A.]]
 [[Category: Barstad, D.]]
-[[Category: Greene, G.L.]]
+[[Category: Greene, G L.]]
-[[Category: Katzenellenbogen, B.S.]]
+[[Category: Katzenellenbogen, B S.]]
-[[Category: Katzenellenbogen, J.A.]]
+[[Category: Katzenellenbogen, J A.]]
-[[Category: Meyers, M.J.]]
+[[Category: Meyers, M J.]]
-[[Category: Nettles, K.W.]]
+[[Category: Nettles, K W.]]
-[[Category: Radek, J.T.]]
+[[Category: Radek, J T.]]
-[[Category: Shiau, A.K.]]
+[[Category: Shiau, A K.]]
 [[Category: ETC]]
 [[Category: antagonist]]
@@ Line 29: / Line 28: @@
 [[Category: transcription factor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:56:33 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:40:34 2008''