在Mps1 MAPK上对共同对接点和ATP结合点的组合准,用于对病原性真菌进行管理
Zhiwei Kong1,2, Saijie Li1,2, Juxian Li1,2
1State Key Laboratory of Maize Bio-breeding, Joint International Research Laboratory of Crop Molecular Breeding, China Agricultural University, Beijing 100193, China.
Journal of agricultural and food chemistry
|December 2, 2024
概括
一种新的杀菌剂TAK-733针对病原性真菌中的Mps1 MAPK. 它通过结合到一个独特的部位来起作用,为对抗真菌病的联合治疗提供了一种新的方法.
科学领域:
- 农业科学 农业科学
- 生物化学 生物化学
- 菌类学 菌类学是指菌类学.
背景情况:
- 菌类耐药性需要具有新作用机制的新型杀菌剂.
- *Magnaporthe oryzae*中的Mps1 MAPK是杀菌剂开发的关键目标.
- 爆病是由Magnaporthe oryzae引起的,对全球粮食安全构成重大威胁.
研究的目的:
- 为了确定针对Mps1 MAPK的新型化合物.
- 为了研究化合物TAK-733.3的作用机制.
- 评估TAK-733与现有的杀菌剂结合使用的潜力.
主要方法:
- 复合选用于识别Mps1 MAPK交互器.
- 生物化学测试以确定结合部位 (ATP竞争性与常见的对接部位).
- 在体内对TAK-733与其他抑制剂结合的疗效研究.
主要成果:
- 化合物PLX-4720和TAK-733被确定为Mps1 MAPK相互作用体.
- PLX-4720作为一种ATP竞争性抑制剂.
- TAK-733与Mps1的共同对接点 (CD) 结合,与ATP结合口袋不同.
- 在体内,TAK-733与ATP竞争性抑制剂PLX-4720和A378-0相结合时表现出协同效应.
结论:
- TAK-733代表了一种具有独特作用机制的新型真菌杀菌剂候选剂.
- 由于TAK-733能够结合CD位点,因此可以与ATP竞争性抑制剂进行联合治疗.
- 这种组合策略对控制致病真菌和克服杀真菌剂耐药性充满希望.
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