首页|甲基赤藓糖醇磷酸胞苷酰转移酶及其抑制剂研究进展

甲基赤藓糖醇磷酸胞苷酰转移酶及其抑制剂研究进展

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甲基赤藓糖醇磷酸(methylerythritol phosphate,MEP)途径是生产萜类化合物前体异戊二烯基二磷酸(isopentenyl diphosphate,IPP)和二甲基烯丙基二磷酸(dimethylallyl diphosphate,DMAPP)必要的生化途径之一,该途径广泛存在于植物、细菌及病原体体内,而哺乳动物中不存在。MEP途径包含的 7 个关键酶都可以作为新型农药和医药的作用靶标。甲基赤藓糖醇磷酸胞苷酰转移酶(2-C-methyl-D-erythritol-4-phosphate cytidyltransferase,IspD)是MEP途径的第三个关键酶,它的活性位点亲脂性低,但拥有独特的变构位点,近年来引起研究人员的广泛关注。利用IspD小分子抑制剂来阻断MEP通路,从而间接地抑制萜类化合物的生成,可以造成病菌和植物的死亡,达到杀菌或除草目的。本文对IspD结构、催化机理、IspD抑制剂及其作用机制等内容进行了综述,可为以IspD作为靶标的抑制剂的筛选以及新型农药和医药的开发提供指导。
Research progress of 2-C-methyl-D-erythritol-4-phosphate cytidyltransferase and its inhibitors
MEP(methylerythritol phosphate)pathway is one of the essential biochemical pathways for the production of the terpenoid precursors isoprenyl diphosphate(IPP)and dimethylallyl diphosphate(DMAPP),and is widespread in plants,bacteria,and pathogens,but absent in mammals.The seven key enzymes of the MEP pathway have been identified as targets for the development of novel pesticides and pharmaceuticals.2-C-methyl-D-erythritol-4-phosphate cytidyltransferase(IspD)is the third key enzyme of the MEP pathway,which has a low lipophilicity of active sites but unique allosteric sites that have attracted considerable attention from researchers in recent years.Using small molecule inhibitors of IspD to block the MEP pathway and indirectly inhibit the generation of terpenoids can cause the death of pathogens and plants to achieve the purpose of sterilization or weeding.This paper reviews the structure,mechanism,IspD inhibitors and mode of action of the IspD protease.The aim is to provide guidance for the screening of inhibitors targeting IspD and the development of novel pesticides and pharmaceuticals.

MEP pathwayIspDallosteric sitesmall molecule inhibitors

王吉利、陈灿、周雅情、吴文海、孙勇、王星、陈杰

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汉江师范学院化学与环境工程学院,湖北十堰 442000

浙江农林大学化学与材料工程学院,杭州 311300

浙江农林大学林业与生物技术学院,杭州 311300

甲基赤藓糖醇磷酸途径 甲基赤藓糖醇磷酸胞苷酰转移酶 变构位点 小分子抑制剂

湖北省教育厅科学研究计划中青年人才湖北省自然科学基金国家自然科学基金

Q202231032022CFB85432101228

2024

农药学学报
中国农业大学

农药学学报

CSTPCD北大核心
影响因子:0.879
ISSN:1008-7303
年,卷(期):2024.26(4)