title: ERRgamma tethers strongly bisphenol A and 4-alpha-cumylphenol in an induced-fit manner.
abstract: A receptor-binding assay and X-ray crystal structure analysis demonstrated that the endocrine disruptor bisphenol A (BPA) strongly binds to human estrogen-related receptor gamma (ERRgamma). BPA is well anchored to the ligand-binding pocket, forming hydrogen bonds with its two phenol-hydroxyl groups. In this study, we found that 4-alpha-cumylphenol lacking one of its phenol-hydroxyl groups also binds to ERRgamma very strongly. The 2.0 A crystal structure of the 4-alpha-cumylphenol/ERRgamma complex clearly revealed that ERRgamma's Leu345-beta-isopropyl plays a role in the tight binding of 4-alpha-cumylphenol and BPA, rotating in a back-and-forth induced-fit manner.
authors.affiliation: Laboratory of Structure-Function Biochemistry, Department of Chemistry, The Research-Education Centre of Risk Science, Faculty and Graduate School of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Matsushima
authors.forename: Takamasa
authors.initials: T
authors.lastname: Teramoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okada
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Tokunaga
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Kakuta
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shimohigashi
mesh_terms: D001559:Benzhydryl Compounds; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D006860:Hydrogen Bonding; D007930:Leucine / Q000737:chemistry; D008024:Ligands; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D007930:Leucine; D008024:Ligands; D010636:Phenols; D011960:Receptors, Estrogen; C490917:ESRRG protein, human; C516284:4-cumylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds