毛兰素与其潜在靶点蛋白丙酮酸羧化酶的相互作用研究  

Studies on interaction between erianin and its potential target protein,pyruvate carboxylase

作　　者：谢泽宇 陈水玲 杨志华 阮子静 黄新河[1] XIE Ze-yu;CHEN Shui-ling;YANG Zhi-hua;RUAN Zi-jing;HUANG Xin-he(School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,China)

机构地区：[1]西南交通大学生命科学与工程学院,成都610031

出　　处：《生物学杂志》2020年第4期17-20,共4页Journal of Biology

基　　金：四川省科技厅应用基础研究项目(No.2016JY0113)。

摘　　要：为考察毛兰素与人丙酮酸羧化酶(hPC)的相互作用,为阐明其药理毒理作用奠定基础,采用计算机分子模拟对接初步预测毛兰素与hPC的结合及相互作用强度,并采用线粒体蛋白孵育体系,在体外验证毛兰素对hPC酶活性的影响。结果显示,毛兰素可在多个位点与hPC结合。最佳结合Pose在四聚体蛋白AD界面和BC界面处,毛兰素的三甲氧基苯基通过π-二硫键与π-烷基互作同hPC甲硫氨酸残基(B:804)结合,其主体苯环则通过常规氢键与π-阴离子互作同hPC的天冬氨酸残基(C:774)结合,此外,还有多个甲氧基与hPC有着碳氢非键相互作用。同时,体外抑制实验表明毛兰素对hPC具有显著抑制作用,且呈剂量依赖性,与分子对接结果一致。结果表明,毛兰素能与hPC相互结合,并抑制其酶活性。This study aimed to investigate the interaction between erianin and human pyruvate carboxylase(hPC),and thus lay a foundation for elucidating its pharmacology and toxicology.Computer molecular simulation docking was employed to predict the binding and interaction intensity of erianin and hPC,furthermore,mitochondrial protein incubation system was used to verify the effect of erianin on hPC activity in vitro.Molecular docking results showed that erianin could bind to hPC at multiple sites.The best binding poses were AD interface and BC interface of the tetramer protein,the trimethoxyphenyl group of erianin interacted with the hPC methionine(B:804)residue via aπ-sulfur and aπ-alkyl interaction,the main benzene ring interacted with the aspartic acid(C:774)residue of hPC through hydrogen bonding andπ-anion interaction,and there were also multiple methoxy groups that had a hydrocarbon-non-bond interaction with hPC.Consistently,In vitro inhibition experiments showed that erianin had a significant inhibitory effect on hPC in a dose-dependent manner.Collectively,the experiments showed that the binding of erianin and hPC,and also erianin treatment inhibited the enzyme activity of hPC.

关 键 词：毛兰素 丙酮酸羧化酶 分子对接 相互作用 

分 类 号：Q255[生物学—细胞生物学]