Distinction of the binding modes for human nuclear receptor ERR between bisphenol A and 4-hydroxytamoxifen

• DOI: 10.1093/jb/mvq056
• Publication Date: 2010-06-12T00:25:48Z
• Authors: X. Liu; A. Matsushima; H. Okada; Y. Shimohigashi
• Keywords: 0301 basic medicine; Tamoxifen; 03 medical and health sciences; Binding Sites; Phenols; Receptors, Estrogen; Humans; Hydrogen Bonding; Benzhydryl Compounds; Protein Binding

Bisphenol A (BPA) strongly binds to human estrogen-related receptor γ (ERRγ). BPA is an oestrogenic endocrine disruptor that influences various physiological functions at very low doses. as inverse-type antagonist of ERRγ retain its high basal constitutive activity by inhibiting the deactivating inverse agonist 4-hydroxytamoxifen (4-OHT). We recently demonstrated residues Glu275 and Arg316 function intrinsic binding site BPA's phenol-hydroxyl group. also determined chief importance phenol-hydroxyl↔Arg316 hydrogen bonding corroborative role phenol-hydroxyl↔Glu275 bonding. However, there appeared be a distinct difference between modes 4-OHT. In present study, using tritium-labelled or non-labelled 4-OHT, we evaluated in detail capabilities wild-type mutants with amino acid alterations positions 275 316. Both compounds exhibited strong ability due Arg316. 4-OHT revealed significantly reduced occupancy for both mutant receptors. The data obtained suggest barely recruit phenol compounds.