Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma.
Article Details
- CitationCopy to clipboard
Babu S, Vellore NA, Kasibotla AV, Dwayne HJ, Stubblefield MA, Uppu RM
Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma.
Biochem Biophys Res Commun. 2012 Sep 21;426(2):215-20. doi: 10.1016/j.bbrc.2012.08.065. Epub 2012 Aug 23.
- PubMed ID
- 22935422 [ View in PubMed]
- Abstract
A xenoestrogen and known endocrine disruptor, bisphenol A (BPA) binds the human estrogen-related receptor-gamma (ERRgamma) with high affinity (Kd approximately 5.5 nM). It is likely that BPA undergoes oxidative biotransformation by hypochlorite/hypochlorous acid ((-)OCl/HOCl) and peroxynitrite (PN) and the products formed in these reactions may serve as secondary estrogens and contribute to the toxicodynamics of BPA. Therefore, in the present study we have examined the formation of chlorinated and nitrated BPA in reactions of BPA with (-)OCl/HOCl and PN(+CO(2)) performed around the neutral pH. We have identified four major products in these reactions and they include 3-chloro-BPA (CBPA), 3,3'-dichloro-BPA (DCBPA), 3-nitro-BPA (NBPA) and 3,3'-dinitro-BPA (DNBPA). Towards understanding the toxicodynamics and estrogenic activity of BPA in biological systems, we have performed molecular docking of BPA, CBPA, DCBPA, DNBPA and NBPA onto the ERRgamma using AutoDock 4.2 software and compared the binding energies with those of estradiol, the natural ligand. Based on the genetic algorithm, the three best conformations were selected and averaged for each ligand and a detailed analysis of molecular interactions based on free energies of binding (kcal/mol) was computed. The results indicate the following rank order of binding to ERRgamma: BPA (-8.78 +/- 0.06) > CBPA (-8.53 +/- 0.41) > NBPA (-7.36 +/- 0.74) > DCBPA (-5.24 +/- 0.17) > DNBPA (-4.95 +/- 0.78) > estradiol (-4.94 +/- 1.04). The docking studies revealed that the OH group of one of the phenyl rings forms a hydrogen bond with Glu275/Arg316, while the OH group of other phenyl ring was bound to Asp346. These results suggest that both BPA and its putative chlorinated and nitrated metabolites have strong binding affinity compared to estradiol.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Estradiol acetate Estrogen-related receptor gamma Protein Humans UnknownLigandDetails Estradiol benzoate Estrogen-related receptor gamma Protein Humans UnknownLigandDetails Estradiol cypionate Estrogen-related receptor gamma Protein Humans UnknownLigandDetails Estradiol dienanthate Estrogen-related receptor gamma Protein Humans UnknownLigandDetails Estradiol valerate Estrogen-related receptor gamma Protein Humans UnknownLigandDetails