2P15

Crystal structure of the ER alpha ligand binding domain with the agonist ortho-trifluoromethylphenylvinyl estradiol

Summary for 2P15

• Entry DOI: 10.2210/pdb2p15/pdb
• Descriptor: Estrogen receptor, GRIP peptide, (17BETA)-17-{(E)-2-[2-(TRIFLUOROMETHYL)PHENYL]VINYL}ESTRA-1(10),2,4-TRIENE-3,17-DIOL, ... (4 entities in total)
• Functional Keywords: nulear receptor, ligand binding domain, helix 12, hormone receptor
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372; Nucleus: Q15596
• Total number of polymer chains: 4
• Total formula weight: 62817.98

Authors

Bruning, J.B.,Nettles, K.W.,Greene, G.L.,Kim, Y. (deposition date: 2007-03-02, release date: 2007-05-01, Last modification date: 2024-02-21)

Primary citation

Nettles, K.W.,Bruning, J.B.,Gil, G.,O'Neill, E.E.,Nowak, J.,Guo, Y.,Kim, Y.,DeSombre, E.R.,Dilis, R.,Hanson, R.N.,Joachimiak, A.,Greene, G.L.
Structural plasticity in the oestrogen receptor ligand-binding domain.
Embo Rep., 8:563-568, 2007

PubMed 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 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.

PubMed: 17468738
DOI: 10.1038/sj.embor.7400963

Experimental method

X-RAY DIFFRACTION (1.94 Å)