tailieunhanh - Báo cáo khoa học: Receptor binding characteristics of the endocrine disruptor bisphenol A for the human nuclear estrogen-related receptor c

Bisphenol A, 2,2-bis(4-hydroxyphenyl)propane, is an estrogenic endocrine disruptor that influences various physiological functions at very low doses, even though bisphenol A itself is ineffectual as a ligand for the estrogen receptor. | ễFEBS Journal Receptor binding characteristics of the endocrine disruptor bisphenol A for the human nuclear estrogen-related receptor c Chief and corroborative hydrogen bonds of the bisphenol A phenol-hydroxyl group with Arg316 and Glu275 residues Xiaohui Liu Ayami Matsushima Hiroyuki Okada Takatoshi Tokunaga Kaname Isozaki and Yasuyuki Shimohigashi Laboratory of Structure-Function Biochemistry Department of Chemistry The Research-Education Centre of Risk Science Faculty and Graduate Schoolof Sciences Kyushu University Fukuoka Japan Keywords bisphenolA estrogen-related receptor c nuclear receptor receptor binding site receptor binding assay Correspondence Y. Shimohigashi Laboratory of StructureFunction Biochemistry Department of Chemistry The Research Education Centre of Risk Science Faculty of Sciences Kyushu University Fukuoka 812-8581 Japan Fax 81 92 642 2584 Tel 81 92 642 2584 E-mail shimoscc@ Received 3 September 2007 revised 14 October 2007 accepted 17 October 2007 doi Bisphenol A 2 2-bis 4-hydroxyphenyl propane is an estrogenic endocrine disruptor that influences various physiological functions at very low doses even though bisphenol A itself is ineffectual as a ligand for the estrogen receptor. We recently demonstrated that bisphenol A binds strongly to human estrogen-related receptor c one of 48 human nuclear receptors. Bisphenol A functions as an inverse antagonist of estrogen-related receptor c to sustain the high basal constitutive activity of the latter and to reverse the deactivating inverse agonist activity of 4-hydroxytamoxifen. However the intrinsic binding mode of bisphenol A remains to be clarified. In the present study we report the binding potentials between the phenol-hydro-xyl group of bisphenol A and estrogen-related receptor c residues Glu275 and Arg316 in the ligand-binding domain. By inducing mutations in other amino acids we evaluated the change in receptor binding capability of .