A computational insight into endocrine disruption by polychlorinated biphenyls via non-covalent interactions with human nuclear receptors

• Published in: Ecotoxicology and environmental safety Vol. 214; p. 112086
• Main Authors: Akinola, Lukman K., Uzairu, Adamu, Shallangwa, Gideon A., Abechi, Stephen E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2021; Elsevier
• Subjects: Androgens; Endocrine disruptor; Endocrine Disruptors - metabolism; Endocrine Disruptors - toxicity; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta; Humans; Hydrogen Bonding; Ligands; Molecular Conformation; Molecular docking; Molecular Docking Simulation; Non-covalent interaction; Nuclear receptor; Polychlorinated biphenyls; Polychlorinated Biphenyls - metabolism; Polychlorinated Biphenyls - toxicity; Receptors, Androgen - metabolism; Receptors, Thyroid Hormone - metabolism; Thyroid Hormones; Polychlorinated biphenyls; Nuclear receptor; Endocrine disruptor; Non-covalent interaction; Molecular docking
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.112086

Production of polychlorinated biphenyls (PCBs) was banned a long time ago because of their harmful health effects but humans continue to be exposed to residual PCBs in the environment. In this study, the susceptibility of human nuclear receptors to binding by PCBs was investigated using molecular docking simulation. Findings revealed that PCBs belonging to ortho-substituted, mono-ortho-substituted and non-ortho-substituted congeners could bind to agonistic conformations of androgen (AR), estrogen (ER α and ER β), glucocorticoid (GR) and thyroid hormone (TR α and TR β) receptors as well as antagonistic conformation of androgen receptor (AR an) but only ortho-substituted and mono-ortho-substituted PCBs could bind to estrogen receptors in their antagonistic conformations (ER α an and ER β an). Further molecular docking analyses showed that PCBs mimic the modes of interaction observed for the co-crystallized ligands in the crystal structures of the affected receptors, utilizing 81%, 83%, 78%, 60%, 75%, 60%, 86%, 100% and 75% of the amino acid residues utilized by the co-crystallized ligands for binding in AR, AR an, ER α, ER α an, ER β, ER β an, GR, TR α and TR β respectively. This computational study suggests that PCBs may cause endocrine disruption via formation of non-covalent interactions with androgen, estrogen, glucocorticoid and thyroid hormone receptors. [Display omitted] •Susceptibility of 12 nuclear receptors to binding by PCBs was investigated in silico.•Steroid and thyroid hormone receptors were found to be susceptible to binding by PCBs.•PCBs may cause endocrine disruption in humans via nuclear receptor binding.