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Type: Journal article
Title: Structural plasticity in the oestrogen receptor ligand-binding domain
Author: Nettles, K.
Bruning, J.
Gil, G.
O'Neill, E.
Nowak, J.
Hughs, A.
Kim, Y.
DeSombre, E.
Dilis, R.
Hanson, R.
Joachimiak, A.
Greene, G.
Citation: EMBO Reports, 2007; 8(6):563-568
Publisher: Nature Publishing Group
Issue Date: 2007
ISSN: 1469-221X
Statement of
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
RMID: 0020121331
DOI: 10.1038/sj.embor.7400963
Appears in Collections:Molecular and Biomedical Science publications

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