摘要
应用分子对接方法探讨了多溴二苯醚(PBDE)衍生物与人胎盘芳香化酶间的可能作用机理.通过分析对接生成的构象发现,羟基多溴二苯醚(HO-PBDEs)和甲氧基多溴二苯醚(Me O-PBDEs)与人胎盘芳香化酶间形成氢键的情况不同.对人胎盘芳香化酶有抑制活性的HO-PBDEs通过其羟基(—OH)与氨基酸残基Arg435、Arg115、Arg375、Asp309和Ala306形成氢键,而对人胎盘芳香化酶无抑制活性的Me O-PBDEs的甲氧基(Me O—)几乎不与芳香化酶内氨基酸残基形成氢键,这可能是二者对芳香化酶抑制活性不同的原因.由此推测,化合物作为氢键供体可能是多溴二苯醚衍生物具有抑制芳香化酶活性的结构基础.本研究从化合物结构及化合物与人胎盘芳香化酶结合的构象特征上解释化合物活性不同的原因,以期能够利用构象分析得到的结果进行筛选.
Intermolecular interaction between polybrominated diphenyl ether （ PBDE ） derivatives and human placental aromatase was explored based on molecular docking.This study revealed that the H-bond interactions between PBDE derivatives and aromatase are different. HO-PBDEs, having significant inhibition on placental aromatase activity, formed H-bonds between—OH and amino acid residues Arg435, Arg115, Arg375, Asp309 and Ala306. MeO-PBDEs, not having inhibition activity on aromatase enzyme, did not form H-bond between MeO— and amino acid residues. So it was presumed that hydrogen bond donor may be the structural basis of PBDE derivatives having aromatase inhibition. The present study explored the structural and conformational requirements of PBDE derivatives with different aromatase inhibition activities.It is hoped that further screening can be carried out by analyzing the poses derived from molecular docking.
出处
《环境化学》
CAS
CSCD
北大核心
2015年第5期904-910,共7页
Environmental Chemistry
基金
江苏省环保科研课题(2013034)
国家自然科学基金项目(20737001)
徐州市科技项目(XM13B110)资助
关键词
多溴二苯醚衍生物
芳香化酶
分子间作用
分子对接
polybrominated diphenyl ether （ PBDE） derivatives
aromatase enzyme
intermolecular interaction
molecular docking
