您好，欢迎访问上海市农业科学院 机构知识库！
上海市农业科学院机构知识库

全部

  • 全部
  • 标题
  • 学者
  • 机构
  • 关键词

Discovery of a Manduca sexta Allatotropin Antagonist from a Manduca sexta Allatotropin Receptor Homology Model

文献类型： 外文期刊

作者： Kai, Zhen-Peng 1 ; Zhu, Jing-Jing 1 ; Deng, Xi-Le 3 ; Yang, Xin-Ling 3 ; Chen, Shan-Shan 2 ;

作者机构： 1.Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China

2.Shanghai Acad Agr Sci, Inst Agrofood Stand & Testing Technol, Shanghai 201403, Peoples R China

3.China Agr Univ, Dept Appl Chem, Coll Sci, Beijing 100193, Peoples R China

关键词： allatotropin; insecticide; GPCR; antagonist

期刊名称：MOLECULES （ 影响因子：4.411； 五年影响因子：4.587 ）

ISSN： 1420-3049

年卷期： 2018 年 23 卷 4 期

页码：

收录情况： SCI

摘要： Insect G protein coupled receptors (GPCRs) have important roles in modulating biology, physiology and behavior. They have been identified as candidate targets for next-generation insecticides, yet these targets have been relatively poorly exploited for insect control. In this study, we present a pipeline of novel Manduca sexta allatotropin (Manse-AT) antagonist discovery with homology modeling, docking, molecular dynamics simulation and structure-activity relationship. A series of truncated and alanine-replacement analogs of Manse-AT were assayed for the stimulation of juvenile hormone biosynthesis. The minimum sequence required to retain potent biological activity is the C-terminal amidated octapeptide Manse-AT (6-13). We identified three residues essential for bioactivity (Thr(4), Arg(6) and Phe(8)) by assaying alanine-replacement analogs of Manse-AT (6-13). Alanine replacement of other residues resulted in reduced potency but bioactivity was retained. The 3D structure of the receptor (Manse-ATR) was built and the binding pocket was identified. The binding affinities of all the analogs were estimated by calculating the free energy of binding. The calculated binding affinities corresponded to the biological activities of the analogs, which supporting our localization of the binding pocket. Then, based on the docking and molecular dynamics studies of Manse-AT (10-13), we described it can act as a potent Manse-AT antagonist. The antagonistic effect on JH biosynthesis of Manse-AT (10-13) validated our hypothesis. The IC50 value of antagonist Manse-AT (10-13) is 0.9 nM. The structure-activity relationship of antagonist Manse-AT (10-13) was also studied for the further purpose of investigating theoretically the structure factors influencing activity. These data will be useful for the design of new Manse-AT agonist and antagonist as potential pest control agents.

  • 相关文献
作者其他论文 更多>>
置顶
购物车
反馈

© 京ICP备09089781号-29 主办单位：上海市农业科学院

学术资源： 中国农业科学院 农业专业知识服务系统 农科联盟资源共建共享平台 中国农业科技文献与信息服务平台 中国农业期刊集成服务平台