Interaction mechanisms of the binding of polychlorinated biphenyls to thyroid hormone transporters revealed based on quantum chemistry and spectroscopy

作者：Miao, Wangli; Jia, Dan; Rui, Yuefan; Liang, Wenhui; Chen, Yanting; Liu, Hongyan; Yi, Zhongsheng^*

来源：Journal of Molecular Structure, 2023, 1281: 135104.

DOI：10.1016/j.molstruc.2023.135104

• Thyroid hormone transport protein
• Polychlorinated biphenyls
• Spectroscopy
• Molecular dynamics simulation
• Molecular docking

Polychlorinated biphenyls (PCBs) are a kind of persistent, bioaccumulative and refractory environmen-tal pollutants. In this work, three typical PCBs (CB54, CB125, CB152) were selected to investigate the interaction between thyroid hormone (TH) transporter and PCBs by combining spectroscopy and calcula-tion. The fluorescence results showed that PCBs had a high binding affinity to TH transport proteins and strongly quenched the intrinsic fluorescence of TH transport proteins through a static quenching mecha-nism. Analysis of thermodynamic parameters revealed that hydrophobic interactions played an important role in the complex formation. Furthermore, the microenvironment and conformation of transthyretin (TTR) and thyroxine binding globulin (TBG) were altered in the presence of PCBs, which was confirmed by Fourier transform infrared (FT-IR) spectroscopy and quantum chemical analysis. Finally, the optimal binding mode of PCBs to TH transport proteins and the stability of the complexes were studied through molecular docking and molecular dynamics simulations.

• 单位
  桂林理工大学