In silico study of molecular mechanisms of action: Estrogenic disruptors among phthalate esters

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 中国科学院饮用水科学与技术重点实验室

	In silico study of molecular mechanisms of action: Estrogenic disruptors among phthalate esters
	Zhu, Qian ; Liu, Lanhua ; Zhou, Xiaohong ; Ma, Mei
刊名	ENVIRONMENTAL POLLUTION
	2019-12-01
卷号	255 页码:-
关键词	In silica Phthalate esters Human estrogen receptor alpha
ISSN号	0269-7491
英文摘要	Phthalate esters (PAEs), as widely used plasticizers, have been concerned for their possible disruption of estrogen functions via binding to and activating the transcription of estrogen receptors (ERs). Nevertheless, the computational interpretation of the mechanism of ERs activities modulated by PAEs at the molecular level is still insufficient, which hinders the reliable screening of the ERs-active PAEs with high speed and high throughput. To bridge the gap, the in silico simulations considering the effects of coactivators were accomplished to explore the molecular mechanism of action for the purpose of predicting the estrogenic potencies of PAEs. The transcriptional activation functions of human ER alpha (hER alpha) modulated by PAEs is predicted via the simulations including binding interaction of PAEs and hER alpha conformational changes of PAEs-hER alpha complexes and recruitment of coactivators. Molecular insight into the diverse estrogen mechanism of action among PAEs with regard to hER alpha agonists and selective estrogen receptor modulators (SERMs) is provided. Agonist-modulated conformational change of hER alpha leads to the optimal exposure of its Activation Function 2 (AF-2) surface which, in turn, facilitates the recruitment of coactivators, therefore promoting the transcriptional activation functions of hER alpha. Conversely, binding interaction of hER alpha with SERMs among PAEs leads to the conformational change with blocked AF-2 surface, thus preventing the recruitment of coactivators and consequently inhibiting the AF-2 activity. The two-hybrid recombinant yeast is experimentally used for verification. The established in silico evaluation methodology exhibits great promise to speed up the prediction of chemicals which work as hER alpha agonist or SERMs. (C) 2019 Elsevier Ltd. All rights reserved.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/43475]
专题	生态环境研究中心_中国科学院饮用水科学与技术重点实验室
作者单位	1.Univ Chinese Acad Sci, Coll Resources & Environm, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, Key Lab Drinking Water Sci & Technol, Beijing 100085, Peoples R China 3.Tsinghua Univ, Sch Environm, State Key Joint Lab ESPC, Beijing 100084, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Qian,Liu, Lanhua,Zhou, Xiaohong,et al. In silico study of molecular mechanisms of action: Estrogenic disruptors among phthalate esters[J]. ENVIRONMENTAL POLLUTION,2019,255:-.
APA	Zhu, Qian,Liu, Lanhua,Zhou, Xiaohong,&Ma, Mei.(2019).In silico study of molecular mechanisms of action: Estrogenic disruptors among phthalate esters.ENVIRONMENTAL POLLUTION,255,-.
MLA	Zhu, Qian,et al."In silico study of molecular mechanisms of action: Estrogenic disruptors among phthalate esters".ENVIRONMENTAL POLLUTION 255(2019):-.