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Editor’s Highlight: Structure-Based Investigation on the Binding and Activation of Typical Pesticides With Thyroid Receptor.

Editor’s Highlight: Structure-Based Investigation on the Binding and Activation of Typical Pesticides With Thyroid Receptor.
Author Information (click to view)

Xiang D, Han J, Yao T, Wang Q, Zhou B, Mohamed AD, Zhu G,


Xiang D, Han J, Yao T, Wang Q, Zhou B, Mohamed AD, Zhu G, (click to view)

Xiang D, Han J, Yao T, Wang Q, Zhou B, Mohamed AD, Zhu G,

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Toxicological sciences : an official journal of the Society of Toxicology 160(2) 205-216 doi 10.1093/toxsci/kfx177

Abstract

A broad range of pesticides have been reported to interfere with the normal function of the thyroid endocrine system. However, the precise mechanism(s) of action has not yet been thoroughly elucidated. In this study, 21 pesticides were assessed for their binding interactions and the potential to disrupt thyroid homeostasis. In the GH3 luciferase reporter gene assays, 5 of the pesticides tested had agonistic effects in the order of procymidone > imidacloprid > mancozeb > fluroxypyr > atrazine. 11 pesticides inhibited luciferase activity of T3 to varying degrees, demonstrating their antagonistic activity. And there are 4 pesticides showed mixed effects when treated with different concentrations. Surface plasmon resonance (SPR) biosensor technique was used to directly measure the binding interactions of these pesticides to the human thyroid hormone receptor (hTR). 13 pesticides were observed to bind directly with TR, with a KD ranging from 4.80E-08 M to 9.44E-07 M. The association and disassociation of the hTR/pesticide complex revealed 2 distinctive binding modes between the agonists and antagonists. At the same time, a different binding mode was displayed by the pesticides showed mix agonist and antagonist activity. In addition, the molecular docking simulation analyses indicated that the interaction energy calculated by CDOCKER for the agonists and antagonists correlated well with the KD values measured by the surface plasmon resonance assay. These results help to explain the differences of the TR activities of these tested pesticides.

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