Perfluorinated compounds binding to estrogen receptor of different species: a molecular dynamic modeling
- 103 Downloads
Perfluorinated compounds (PFCs) were widely utilized in commercial and industrial applications, which could interfere with the endocrine systems of experimental animals and humans by interacting with estrogen receptors (ERs). Considering the possible differential binding preferences and relative binding affinities of PFCs to ERs of humans and other species, a cross-species comparison is necessary to effectively assess the health risk of PFCs to humans. In the present work, the species-specific binding characterizations between two PFCs, including perfluorooctane sulfonate (PFOS) and PFOS(4m, 5m), and the different ERαs from Rattus norvegicus, rainbow trout, and humans were explored based on a molecular dynamic modeling. The results proved that linear perfluorinated compound PFOS could make a much stronger binding to ERαs than the branched perfluorinated compounds PFOS(4m, 5m). In addition, PFOS and PFOS(4m, 5m) presented species-difference among human, Rattus norvegicus, and rainbow trout. The binding affinity with ERα presented an order of human >Rattus norvegicus > rainbow trout. This suggested that PFOS and PFOS(4m, 5m) have the strongest effects on human ERα over the other two species. As a consequence, the PFCs were more sensitive to human ERα than to those of Rattus norvegicus and rainbow trout. This resulted in greater susceptibility to adverse effects, which suggested a possible underestimation of the endocrine-disrupting effects of PFCs in humans. The cross-species comparison represents the first and necessary step to identify species-specific binding mechanisms and to accurately evaluate the potential health risks of PFCs in humans.
KeywordsPerfluorinated compounds (PFCs) Estrogen receptor α (ERα) Molecular dynamics Species difference
This work was financially supported by the National Natural Science Foundation of China (No. 31000017) (No.21207056), State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (KF2015-17), Key Laboratory of Chemistry and Quality for Traditional Chinese Medicines of the University of Gansu Province, Gansu University of Chinese Medicines (zzy-2016-01), Fundamental Research Funds for the Central Universities (lzujbky-2017-200; lzujbky-2017-kb05; LZU-JZH1914), Gansu Provincial Administration of traditional Chinese Medicine (GZK-2017-63), and Lanzhou talent innovation and entrepreneurship technology program (2016-RC-19).
- 17.Albrecht PP, Torsell NE, Krishnan P, Ehresman DJ, Frame SR, Chang SC, Butenhoff JL, Kennedy GL, Gonzalez FJ, Peters JM (2013) A species difference in the peroxisome proliferator-activated receptor α-dependent response to the developmental effects of perfluorooctanoic acid. Toxicol Sci 131(2):568–582CrossRefGoogle Scholar
- 21.da Silva Lima CH, de Alencastro RB, Kaiser CR, de Souza MV, Rodrigues CR, Albuquerque MG (2015) Aqueous molecular dynamics simulations of the M. tuberculosis Enoyl-ACP reductase-NADH system and its complex with a substrate mimic or diphenyl ethers inhibitors. Int J Mol Sci 16(10):23695–23722CrossRefGoogle Scholar