Experimental and computational insights on the recognition mechanism between the estrogen receptor alpha with bisphenol compounds
文献类型：期刊论文
| 作者 | Song, Maoyong; Cao, Huiming; Wang, Fengbang; Liang, Yong; Wang, Hailin; Zhang, Aiqian |
| 刊名 | ARCHIVES OF TOXICOLOGY
 |
| 出版日期 | 2017-09-01 |
| 卷号 | 91期号:12页码:3897-3912 |
| 关键词 | Estrogen Receptor Alpha Bisphenols Estrogenic Activity Molecular Dynamics Simulations |
| 英文摘要 | Certain bisphenols (BPs) have been regarded as endocrine-disrupting chemicals due to their structural similarities to bisphenol A (BPA), a well-known weak estrogenic chemical. However, very limited data are currently available on the relationship between estrogenic activity and the structure of BP analogs. Therefore, we systematically investigated the estrogenic potency of 14 selected BP analogs with typical structures using experimental and computational methods. Most of the tested BP analogs exhibited weak estrogenic activities in both cell proliferation and MVLN assays with the exception of TBBPA, TCBPA and TBBPS. Molecular modeling techniques have been performed to investigate the dynamic structural characteristics of recognition processes between BPs and estrogen receptor alpha (ER alpha) at the atomic level. Thr347 was identified as the key residue responsible for the recognition of TBBPA, TCBPA and TBBPS by means of induced-fit H-bonding interactions in the binding pocket of ER alpha, whereas other BPs, in turn, rely on the alternative formation of H-bonds with His524. Subsequent allosteric modulation interferes significantly with the stability of helix 12 that is crucial for the transcriptional activity of ER alpha. These structural perturbations that are induced by the three compounds were further confirmed to reduce the recruitment potency of co-activators more than other BPs based on calculations of binding free energies, which is in line with observed experimental transcriptional activities. Our findings may help to elucidate the estrogenic potency of BPs with different molecular structures. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/39312]  |
| 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 |
| 推荐引用方式 GB/T 7714 | Song, Maoyong,Cao, Huiming,Wang, Fengbang,et al. Experimental and computational insights on the recognition mechanism between the estrogen receptor alpha with bisphenol compounds[J]. ARCHIVES OF TOXICOLOGY,2017,91(12):3897-3912. |
| APA | Song, Maoyong,Cao, Huiming,Wang, Fengbang,Liang, Yong,Wang, Hailin,&Zhang, Aiqian.(2017).Experimental and computational insights on the recognition mechanism between the estrogen receptor alpha with bisphenol compounds.ARCHIVES OF TOXICOLOGY,91(12),3897-3912. |
| MLA | Song, Maoyong,et al."Experimental and computational insights on the recognition mechanism between the estrogen receptor alpha with bisphenol compounds".ARCHIVES OF TOXICOLOGY 91.12(2017):3897-3912. |
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。