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|Title:||Structural plasticity in the oestrogen receptor ligand-binding domain|
|Citation:||EMBO Reports, 2007; 8(6):563-568|
|Publisher:||Nature Publishing Group|
|Kendall W. Nettles, John B. Bruning, German Gil, Erin E. O’Neill, Jason Nowak, Alun Hughs, Younchang Kim, Eugene R. DeSombre, Robert Dilis, Robert N. Hanson, Andrzej Joachimiak & Geoffrey L. Greene|
|Abstract:||The steroid hormone receptors are characterized by binding to relatively rigid, inflexible endogenous steroid ligands. Other members of the nuclear receptor superfamily bind to conformationally flexible lipids and show a corresponding degree of elasticity in the ligand-binding pocket. Here, we report the X-ray crystal structure of the oestrogen receptor α (ERα) bound to an oestradiol derivative with a prosthetic group, ortho- trifluoromethlyphenylvinyl, which binds in a novel extended pocket in the ligand-binding domain. Unlike ER antagonists with bulky side groups, this derivative is enclosed in the ligand-binding pocket, and acts as a potent agonist. This work shows that steroid hormone receptors can interact with a wider array of pharmacophores than previously thought through structural plasticity in the ligand-binding pocket.|
|Keywords:||oestrogen receptor; structure–activity relationships; nuclear receptors; X-ray crystallography|
|Rights:||©2007 European Molecular Biology Organization|
|Appears in Collections:||Molecular and Biomedical Science publications|
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