Bcs1, a novel target for fungicide.
Bcs1, a novel target for fungicide.
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DOI：
10.3389/fchem.2023.1146753
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
线粒体呼吸链由于其在包括能量代谢在内的各种细胞功能中不可或缺的作用，长期以来一直是开发杀真菌剂的主要目标。多年来，已经发现或开发了多种天然和合成的针对呼吸链复合物的杀真菌剂和杀虫剂，并将其用于农业和医学，这带来了可观的经济收益，但也伴随着对这些化合物的抗性的出现。为了延迟和克服抗性的发生，正在积极寻求用于杀真菌剂开发的新目标。线粒体AAA蛋白Bcs 1是呼吸链复合体III（也称为cyt bc 1复合体）生物发生所必需的，其通过将最后必需的铁硫蛋白亚基以其折叠形式递送至cyt bc 1前复合体。虽然没有报告的表型敲除Bcs 1已在动物中的报告，致病性Bcs 1突变引起的复合物III缺陷和呼吸生长缺陷，这使得它成为一个有前途的新的目标，为发展的杀菌剂。最近的小鼠和酵母Bcs 1的Cryo-EM和X射线结构揭示了Bcs 1的基本寡聚状态，揭示了其底物ISP的易位机制，并为基于结构的药物设计提供了基础。本文综述了Bcs 1的结构和功能，提出了Bcs 1作为抗真菌靶标的应用，并展望了以Bcs 1为靶点设计杀菌剂的前景。
The mitochondrial respiratory chain has long been a primary target for the development of fungicides for its indispensable role in various cellular functions including energy metabolism. Over the years, a wide range of natural and synthetic fungicides and pesticides targeting the respiratory chain complexes have been discovered or developed and used in agriculture and in medicine, which brought considerable economic gains but was also accompanied by the emergence of resistance to these compounds. To delay and overcome the onset of resistance, novel targets for fungicides development are actively being pursued. Mitochondrial AAA protein Bcs1 is necessary for the biogenesis of respiratory chain Complex III, also known as cyt bc 1 complex, by delivering the last essential iron-sulfur protein subunit in its folded form to the cyt bc 1 precomplex. Although no report on the phenotypes of knock-out Bcs1 has been reported in animals, pathogenic Bcs1 mutations cause Complex III deficiency and respiratory growth defects, which makes it a promising new target for the development of fungicides. Recent Cryo-EM and X-ray structures of mouse and yeast Bcs1 revealed the basic oligomeric states of Bcs1, shed light on the translocation mechanism of its substrate ISP, and provided the basis for structure-based drug design. This review summarizes the recent progress made on understanding the structure and function of Bcs1, proposes the use of Bcs1 as an antifungal target, and provides novel prospects for fungicides design by targeting Bcs1.
DOI：
10.1111/febs.15576
发表时间：
2021-05
期刊：
The FEBS journal
影响因子：
--
作者：
Xia D
通讯作者：
Xia D