2p15
Crystal structure of the ER alpha ligand binding domain with the agonist ortho-trifluoromethylphenylvinyl estradiol
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OverviewOverview
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, (ERalpha) 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.
About this StructureAbout this Structure
2P15 is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural plasticity in the oestrogen receptor ligand-binding domain., Nettles KW, Bruning JB, Gil G, O'Neill EE, Nowak J, Guo Y, Kim Y, DeSombre ER, Dilis R, Hanson RN, Joachimiak A, Greene GL, EMBO Rep. 2007 Jun;8(6):563-8. Epub 2007 Apr 27. PMID:17468738
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