Molecular interactions of thyroxine binding globulin and thyroid hormone receptor with estrogenic compounds 4-nonylphenol, 4-tert-octylphenol and bisphenol A metabolite (MBP)

Endocrine disruption due to environmental chemical contaminants is a global human health issue. The aim of present study was to investigate the structural binding aspects of possible interference of commonly detected environmental contaminants on thyroid function. Three compounds, 4-tert-octylphenol (4-tert-OP), 4-nonylphenol (4-NP), and 4-methyl-2,4-bis(4-hydroxypentyl)pent-1-ene (MBP) were subjected to induced fit docking (IFD) against thyroxine binding globulin (TBG) and thyroid hormone receptor (THR). Structural analysis included molecular interactions of the amino acid residues and binding energy estimation between the ligands and the target proteins. All the ligands were successfully placed in the ligand binding pocket of TBG and THR using induced fit docking (IFD). The IFD results revealed high percentage of commonality in interacting amino acid residues between the aforementioned compounds and the native ligand for both TBG and THR. The results of our study further revealed that all the compounds have the potential to interfere with thyroid transport and signaling. However, MBP showed higher binding affinity for both TBG and THR, suggesting higher thyroid disruptive potential as compared to 4-t-OP and 4-NP. Furthermore, our results also suggest that the reported disruptive effects of BPA could actually be exerted through its metabolite; MBP. This work implies that all the three compounds 4-NP, 4-t-OP and especially MBP have the potential to interfere with thyroid hormone transport and signaling. This potentially leads to disruption of thyroid hormone function.