3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.

Bisphenol A [BPA] is a widely dispersed environmental chemical that is of much concern because the BPA monomer is a weak transcriptional activator of human estrogen receptor α [ERα] and ERβ in cell culture. A BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene [MBP], has transcriptional acti...

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Autores principales:	Michael E Baker, Charlie Chandsawangbhuwana
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/426a0b47c30248468c18a8201b4fda3f
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spelling	oai:doaj.org-article:426a0b47c30248468c18a8201b4fda3f2021-11-18T08:13:15Z3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.1932-620310.1371/journal.pone.0046078https://doaj.org/article/426a0b47c30248468c18a8201b4fda3f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23056236/?tool=EBIhttps://doaj.org/toc/1932-6203Bisphenol A [BPA] is a widely dispersed environmental chemical that is of much concern because the BPA monomer is a weak transcriptional activator of human estrogen receptor α [ERα] and ERβ in cell culture. A BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene [MBP], has transcriptional activity at nM concentrations, which is 1000-fold lower than the concentration for estrogenic activity of BPA, suggesting that MBP may be an environmental estrogen. To investigate the structural basis for the activity of MBP at nM concentrations and the lower activity of BPA for human ERα and ERβ, we constructed 3D models of human ERα and ERβ with MBP and BPA for comparison with estradiol in these ERs. These 3D models suggest that MBP, but not BPA, has key contacts with amino acids in human ERα and ERβ that are important in binding of estradiol by these receptors. Metabolism of BPA to MBP increases the spacing between two phenolic rings, resulting in contacts between MBP and ERα and ERβ that mimic those of estradiol with these ERs. Mutagenesis of residues on these ERs that contact the phenolic hydroxyls will provide a test for our 3D models. Other environmental chemicals containing two appropriately spaced phenolic rings and an aliphatic spacer instead of an estrogenic B and C ring also may bind to ERα or ERβ and interfere with normal estrogen physiology. This analysis also may be useful in designing novel chemicals for regulating the actions of human ERα and ERβ.Michael E BakerCharlie ChandsawangbhuwanaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e46078 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael E Baker Charlie Chandsawangbhuwana 3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.
description	Bisphenol A [BPA] is a widely dispersed environmental chemical that is of much concern because the BPA monomer is a weak transcriptional activator of human estrogen receptor α [ERα] and ERβ in cell culture. A BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene [MBP], has transcriptional activity at nM concentrations, which is 1000-fold lower than the concentration for estrogenic activity of BPA, suggesting that MBP may be an environmental estrogen. To investigate the structural basis for the activity of MBP at nM concentrations and the lower activity of BPA for human ERα and ERβ, we constructed 3D models of human ERα and ERβ with MBP and BPA for comparison with estradiol in these ERs. These 3D models suggest that MBP, but not BPA, has key contacts with amino acids in human ERα and ERβ that are important in binding of estradiol by these receptors. Metabolism of BPA to MBP increases the spacing between two phenolic rings, resulting in contacts between MBP and ERα and ERβ that mimic those of estradiol with these ERs. Mutagenesis of residues on these ERs that contact the phenolic hydroxyls will provide a test for our 3D models. Other environmental chemicals containing two appropriately spaced phenolic rings and an aliphatic spacer instead of an estrogenic B and C ring also may bind to ERα or ERβ and interfere with normal estrogen physiology. This analysis also may be useful in designing novel chemicals for regulating the actions of human ERα and ERβ.
format	article
author	Michael E Baker Charlie Chandsawangbhuwana
author_facet	Michael E Baker Charlie Chandsawangbhuwana
author_sort	Michael E Baker
title	3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.
title_short	3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.
title_full	3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.
title_fullStr	3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.
title_full_unstemmed	3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.
title_sort	3d models of mbp, a biologically active metabolite of bisphenol a, in human estrogen receptor α and estrogen receptor β.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/426a0b47c30248468c18a8201b4fda3f
work_keys_str_mv	AT michaelebaker 3dmodelsofmbpabiologicallyactivemetaboliteofbisphenolainhumanestrogenreceptoraandestrogenreceptorb AT charliechandsawangbhuwana 3dmodelsofmbpabiologicallyactivemetaboliteofbisphenolainhumanestrogenreceptoraandestrogenreceptorb
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3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.

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