期刊
EMBO REPORTS
卷 8, 期 6, 页码 563-568出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.embor.7400963
关键词
oestrogen receptor; structure-activity relationships; nuclear receptors; X-ray crystallography
资金
- NCI NIH HHS [R01 CA089489, R01 CA081049, 5R01 CA89489, P30 CA014599-32, P30 CA014599, 1R01 CA81049] Funding Source: Medline
- NCRR NIH HHS [RR07707, P41 RR007707] Funding Source: Medline
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 alpha( ER alpha) 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.
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