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ERRgamma tethers strongly bisphenol A and 4-alpha-cumylphenol in an induced-fit manner
Ayami Matsushima1, Takamasa Teramoto, Hiroyuki Okada
1Laboratory 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.
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.
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