title: Atomic-scale investigation of the interactions between tetrabromobisphenol A, tetrabromobisphenol S and bovine trypsin by spectroscopies and molecular dynamics simulations.
abstract: Tetrabromobisphenol A (TBBPA) and its replacement alternative tetrabromobisphenol S (TBBPS) are used widely as brominated flame retardants (BFRs). However, the potential risk of their effects on bovine trypsin remains largely unknown. We investigated the effects of TBBPA and TBBPS to bovine trypsin by the fluorescence spectroscopy, circular dichroism and molecular dynamics (MD) simulations. They statically quenched the intrinsic fluorescence of bovine trypsin in a concentration-dependent mode and caused slight red-shifted fluorescence. The short and long fluorescence lifetime decay components of bovine trypsin were both affected, partly due to the disturbed microenvironmental changes of Trp215. The β-sheet content of bovine trypsin was significantly reduced from 82.4% to 75.7% and 76.6% by TBBPA and TBBPS, respectively, possibly impairing the physiological function of bovine trypsin. TBBPA and TBBPS bind at the 8-anilinonaphthalene-1-sulfonate (ANS) binding site with an association constant of 1.09×10(4) M(-1) and 2.41×10(4) M(-1) at 298 K, respectively. MD simulations revealed that van der Waals interactions and hydrogen bond interactions are dominant for TBBPA, whereas electrostatic interactions are critical for TBBPS. Our in vitro and in silico studies are beneficial to the understanding of risk assessment and future design of environmental benign BFRs.
authors.affiliation: Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Keke
authors.initials: K
authors.lastname: Ding
authors.affiliation: College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.
authors.forename: Huanxin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058, China.
authors.forename: Haifei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Lv
authors.affiliation: Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058, China.
authors.forename: Liumeng
authors.initials: L
authors.lastname: Pan
authors.affiliation: Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058, China. Electronic address: shulin@zju.edu.cn.
authors.forename: Shulin
authors.initials: S
authors.lastname: Zhuang
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D056004:Molecular Dynamics Simulation; D011075:Polybrominated Biphenyls / Q000737:chemistry*; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D014357:Trypsin / Q000737:chemistry*
chemical_list: D011075:Polybrominated Biphenyls; D014357:Trypsin; C020806:tetrabromobisphenol A
keywords: Brominated flame retardants; Conformational change; Fluorescence lifetime; Molecular dynamics simulation; Tachiya model; Trypsin