Protonation state effects of estrogen receptor alpha on the recognition mechanisms by perfluorooctanoic acid and perfluorooctane sulfonate: A computational study
文献类型：期刊论文
| 作者 | Cao, Huiming; Wang, Ling; Liang, Yong; Li, Zhunjie; Feng, Hongru; Sun, Yuzhen; Zhag, Aiqian; Fu, Jianjie
|
| 刊名 | ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
 |
| 出版日期 | 2019-04-30 |
| 卷号 | 171页码:647-656 |
| 关键词 | Estrogen receptor alpha Perfluorooctanoic acid Perfluorooctane sulfonate Protonation state Molecular dynamics simulations |
| ISSN号 | 0147-6513 |
| 英文摘要 | Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been reported to cause adverse health effects on wildlife as well as humans. Numerous studies demonstrated that PFOA and PFOS could interfere with the transcriptional activation of estrogen receptor alpha (ER alpha) by mimicking the function of endogenous ligand, whereas some reports suggested that the two compounds present non-estrogenic activities. These conflicting results bring a confusion to understand their molecular mechanism on the ER alpha-mediated signaling pathway. To address this issue, we performed the molecular docking and molecular dynamics simulations to elaborate the structural characteristics for the binding of PFOA and PFOS to ER alpha. Our results indicated that the two opposite binding orientations were modulated by the protonation states of key residue His524. In sub-acidic condition, PFOA and PFOS prefer to form the H-bonding interactions with the protonated His524, whereas Arg394 provided the H-bonding interactions for stable binding in sub-alkaline condition. Conformational analyses implied that the diverse binding modes were closely related to the conformational propensity of ER alpha for subsequent coactivator recruitment and transcription activation. Generally, our findings provide a flexible strategy to assess the pH impacts of microenvironment on the toxicities of perfluoroalkyl acids by their interactions with proteins. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/42997]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Environm Chem & Ecotoxicol, Ecoenvironm Sci Res Ctr, Beijing 100085, Peoples R China 2.Jianghan Univ, Inst Environm & Hlth, Wuhan 430056, Hubei, Peoples R China 3.Univ Chinese Acad Sci, Coll Resources & Environm, Beijing 100190, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cao, Huiming,Wang, Ling,Liang, Yong,et al. Protonation state effects of estrogen receptor alpha on the recognition mechanisms by perfluorooctanoic acid and perfluorooctane sulfonate: A computational study[J]. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,2019,171:647-656. |
| APA | Cao, Huiming.,Wang, Ling.,Liang, Yong.,Li, Zhunjie.,Feng, Hongru.,...&Fu, Jianjie.(2019).Protonation state effects of estrogen receptor alpha on the recognition mechanisms by perfluorooctanoic acid and perfluorooctane sulfonate: A computational study.ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,171,647-656. |
| MLA | Cao, Huiming,et al."Protonation state effects of estrogen receptor alpha on the recognition mechanisms by perfluorooctanoic acid and perfluorooctane sulfonate: A computational study".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 171(2019):647-656. |
入库方式： OAI收割
来源：生态环境研究中心
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。