1l2j: Difference between revisions

[[Image:1l2j.gif|left|200px]]<br /><applet load="1l2j" size="350" color="white" frame="true" align="right" spinBox="true"  

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'.

1L2J 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].  

[[Category: Agard, D A.]]

[[Category: Greene, G L.]]

[[Category: Katzenellenbogen, B S.]]

[[Category: Katzenellenbogen, J A.]]

[[Category: Meyers, M J.]]

[[Category: Nettles, K W.]]

[[Category: Radek, J T.]]

[[Category: Shiau, A K.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:40:34 2008''