海藻糖合成酶结构及其抑制剂的研究进展  

Advances in structures and inhibitors of trehalose synthetase

作　　者：蒋志洋 韩清 王金娥 朱凯 张婧瑜 邓鸣飞 黄家兴[1] 段红霞[1] JIANG Zhiyang;HAN Qing;WANG Jin'e;ZHU Kai;ZHANG Jingyu;DENG Mingfei;HUANG Jiaxing;DUANG Hongxia(Innovation Center of Pesticide Research,Department of Applied Chemistry,College of Science,China Agricultural University,Beijing 100193,China)

机构地区：[1]中国农业大学理学院应用化学系农药创新中心,北京100193

出　　处：《农药学学报》2021年第2期209-225,共17页Chinese Journal of Pesticide Science

基　　金：国家重点研发计划项目(2017YFD0200504)。

摘　　要：海藻糖是自然界中广泛存在的非还原性二糖,具有重要的生物学功能。除了可作为储能物质参与机体能量代谢外,更重要的是还可作为结构物质参与真菌细胞壁和昆虫体壁的形成,决定病原菌的致病性或调控昆虫的生长发育。海藻糖合成酶主要负责催化海藻糖的生物合成,包括海藻糖-6-磷酸合成酶和海藻糖-6-磷酸磷酸酯酶两个功能域。近年来,越来越多的研究表明海藻糖合成酶将有望成为新农药创制的候选靶标。本文主要综述了海藻糖-6-磷酸合成酶和海藻糖-6-磷酸磷酸酯酶的晶体结构、酶与底物的结合模式和已报道的海藻糖合成酶抑制剂,以期对以海藻糖合成酶为靶标的抑制剂的筛选、先导化合物的设计和改造以及新型农药的开发提供指导。Trehalose is a non-reducing disaccharide, which exists widely in nature and possesses important biological functions. It is not only an energy storage substance participating in energy metabolism, but also a structure substance participating in the formation of fungal cell walls and insect exoskeletons. Meanwhile, trehalose can regulate the pathogenicity of pathogens, and the growth and development of insects. Trehalose synthetase is mainly responsible for catalyzing the biosynthesis of trehalose, which includes two functional domains: trehalose-6-phosphate synthetase and trehalose-6-phosphate phosphatase. More and more recent studies showed that trehalose synthetase has a great potential as a novel target of pesticides. This review summaried the protein crystal structures, substrate binding modes, and chemical structures of reported inhibitors for trehalose-6-phosphate synthetase and trehalose-6-phosphate phosphatase. It is expected to provide guidance for the screening of inhibitors, the design and the modification of lead compounds, and the development of new pesticides targeting trehalose synthetase in the future.

关 键 词：海藻糖合成酶 海藻糖-6-磷酸合成酶 海藻糖-6-磷酸磷酸酯酶 晶体结构 抑制剂 研究进展 

分 类 号：Q51[生物学—生物化学] Q55