TY - JOUR
T1 - ERRγ tethers strongly bisphenol A and 4-α-cumylphenol in an induced-fit manner
AU - Matsushima, Ayami
AU - Teramoto, Takamasa
AU - Okada, Hiroyuki
AU - Liu, Xiaohui
AU - Tokunaga, Takatoshi
AU - Kakuta, Yoshimitsu
AU - Shimohigashi, Yasuyuki
N1 - Funding Information:
This study was supported by the following grants: Health and Labour Sciences Research Grants for Research on Risk of Chemical Substances, from the Ministry of Health, Labor and Welfare of Japan (Y.S.), the Kyushu University Interdisciplinary Program in Education and Projects in Research Development (A.M.), and a grant for the National Project on Protein Structural and Functional Analyses from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. We thank the staff of the SPring-8 BL38B1 and BL41XU beam lines for help with the X-ray diffraction experiments. Atomic coordinates for the structure have been deposited in the Protein Data Bank under accession code 2ZAS for the 4-α-cumylphenol/ERRγ-LBD complex and 2ZBS for apo-ERRγ-LBD.
PY - 2008/8/29
Y1 - 2008/8/29
N2 - 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 γ (ERRγ). 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-α-cumylphenol lacking one of its phenol-hydroxyl groups also binds to ERRγ very strongly. The 2.0 Å crystal structure of the 4-α-cumylphenol/ERRγ complex clearly revealed that ERRγ's Leu345-β-isopropyl plays a role in the tight binding of 4-α-cumylphenol and BPA, rotating in a back-and-forth induced-fit manner.
AB - 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 γ (ERRγ). 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-α-cumylphenol lacking one of its phenol-hydroxyl groups also binds to ERRγ very strongly. The 2.0 Å crystal structure of the 4-α-cumylphenol/ERRγ complex clearly revealed that ERRγ's Leu345-β-isopropyl plays a role in the tight binding of 4-α-cumylphenol and BPA, rotating in a back-and-forth induced-fit manner.
UR - http://www.scopus.com/inward/record.url?scp=48949115132&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48949115132&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.06.050
DO - 10.1016/j.bbrc.2008.06.050
M3 - Article
C2 - 18582436
AN - SCOPUS:48949115132
VL - 373
SP - 408
EP - 413
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -