Structural basis for molecular recognition of G protein-coupled estrogen receptor by selected bisphenols
文献类型：期刊论文
| 作者 | Liu, Xiuchang; Xue, Qiao; Zhang, Huazhou; Fu, Jianjie ; Zhang, Aiqian
|
| 刊名 | SCIENCE OF THE TOTAL ENVIRONMENT
 |
| 出版日期 | 2021-11-01 |
| 卷号 | 793页码:- |
| ISSN号 | 0048-9697 |
| 关键词 | Structure-dependent GPER binding Molecular recognition mechanism Induced-fit effect Molecular dynamics simulations Bisphenols |
| 英文摘要 | Complicated ligand-dependent signaling pathways of bisphenol A (BPA) and its analogues involve not only intranuclear estrogen receptor but also membrane receptor G protein-coupled estrogen receptor (GPER). However, the structural basis for molecular recognition of GPER by the environmental chemicals remains unknown. To reveal the structural dependence of GPER recognition by bisphenols, a systematic molecular dynamics simulation study was performed for selected bisphenols with different electron hybrid orbitals and substituents on their C atoms connecting two phenol rings. BPA was used as a control, bisphenol C(BPC) as an example for a connecting C with sp(2) hybrid orbitals to provide more ligand rigidity, bisphenol E(BPE) and bisphenol F(BPF) for decreased steric hindrance and hydrophobicity around the connecting C, and bisphenol B(BPB) and bisphenol AF(BPAF) for increased hydrophobicity and steric hindrance. All the tested bisphenols can bind with GPER at its classic orthosteric site to obtain GPER-ligand complexes, while van der Waals interactions and direct intermolecular electrostatic energies provide the driving forces for ligand binding. Bulky substituents and structural rigidity of the connecting C dramatically impair hydrogen bonding between GPER and the bisphenols, which results in decreased contribution of both favorable intermolecular hydrogen bonds and unfavorable polar solvation effect to complex stability of BPB and BPC since decreased number of key residues is expected. Increase in substituent lipophilicity enhances the van der Waals interactions and favorable non-polar solvation effect. The six bisphenols of high structural similarity shared two key recognition residues, Leu137(TM3) and Trp272(TM6), the latter of which was in the highly conserved CWxP motif of TM6 and has been reported as key residue for G protein-coupled receptor activation. Based on the obtained knowledge, GPER affinity and relevant toxicity of BPA alternatives can be easily predicted, and the calculated binding free energies are consistent with the available experimental observations. (C) 2021 Elsevier B.V. All rights reserved. |
| 源URL | [https://ir.rcees.ac.cn/handle/311016/46826]  |
| 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.Univ Chinese Acad Sci, Coll Resources & Environm, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Environm, Hangzhou 310012, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Xiuchang,Xue, Qiao,Zhang, Huazhou,et al. Structural basis for molecular recognition of G protein-coupled estrogen receptor by selected bisphenols[J]. SCIENCE OF THE TOTAL ENVIRONMENT,2021,793:-. |
| APA | Liu, Xiuchang,Xue, Qiao,Zhang, Huazhou,Fu, Jianjie,&Zhang, Aiqian.(2021).Structural basis for molecular recognition of G protein-coupled estrogen receptor by selected bisphenols.SCIENCE OF THE TOTAL ENVIRONMENT,793,-. |
| MLA | Liu, Xiuchang,et al."Structural basis for molecular recognition of G protein-coupled estrogen receptor by selected bisphenols".SCIENCE OF THE TOTAL ENVIRONMENT 793(2021):-. |
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。