Structural basis of Fusarium myosin I inhibition by phenamacril
文献类型:期刊论文
作者 | Zhou, Yuxin1,2; Zhou, X. Edward2; Gong, Yuanping1; Zhu, Yuanye1; Cao, Xiaoman1; Brunzelle, Joseph S.3; Xu, H. Eric2,4; Zhou, Mingguo1; Melcher, Karsten2; Zhang, Feng1 |
刊名 | PLOS PATHOGENS |
出版日期 | 2020-03-01 |
卷号 | 16期号:3页码:23 |
ISSN号 | 1553-7366 |
DOI | 10.1371/journal.ppat.1008323 |
通讯作者 | Zhou, Mingguo() ; Melcher, Karsten(karsten.melcher@vai.org) ; Zhang, Feng(fengz@njau.edu.cn) |
英文摘要 | Fusarium is a genus of filamentous fungi that includes species that cause devastating diseases in major staple crops, such as wheat, maize, rice, and barley, resulting in severe yield losses and mycotoxin contamination of infected grains. Phenamacril is a novel fungicide that is considered environmentally benign due to its exceptional specificity; it inhibits the ATPase activity of the sole class I myosin of only a subset of Fusarium species including the major plant pathogens F. graminearum, F. asiaticum and F. fujikuroi. To understand the underlying mechanisms of inhibition, species specificity, and resistance mutations, we have determined the crystal structure of phenamacril-bound F. graminearum myosin I. Phenamacril binds in the actin-binding cleft in a new allosteric pocket that contains the central residue of the regulatory Switch 2 loop and that is collapsed in the structure of a myosin with closed actin-binding cleft, suggesting that pocket occupancy blocks cleft closure. We have further identified a single, transferable phenamacril-binding residue found exclusively in phenamacril-sensitive myosins to confer phenamacril selectivity. Author summary Phenamacril is a recently identified myosin I inhibitor that is a potent and highly species-specific and myosin subtype-selective fungicide. We report the high-resolution structure of the phenamacril-bound myosin I motor domain of the major crop pathogen Fusarium graminearum, providing insight into the molecular mechanism of phenamacril action and resistance. These results are of broad significance for understanding the mode of actions of myosin-based fungicides and for designing novel myosin I inhibitors for crop protection and for treatment of human myosin dysfunction diseases. |
WOS关键词 | SMALL-MOLECULE INHIBITOR ; MOTOR DOMAIN ; BLEBBISTATIN INHIBITION ; FUNGICIDE JS399-19 ; CRYSTAL-STRUCTURE ; ATPASE ACTIVITY ; LEVER ARM ; MECHANISM ; RESISTANCE ; INSIGHTS |
资助项目 | Van Andel Research Institute ; National Science Foundation of China[31730072] ; Fok Ying-Tong Education Foundation[161022] ; Six Talent Peaks Project in Jiangsu Province[NY-035] |
WOS研究方向 | Microbiology ; Parasitology ; Virology |
语种 | 英语 |
出版者 | PUBLIC LIBRARY SCIENCE |
WOS记录号 | WOS:000523706200053 |
源URL | [http://119.78.100.183/handle/2S10ELR8/281059] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Zhou, Mingguo; Melcher, Karsten; Zhang, Feng |
作者单位 | 1.Nanjing Agr Univ, Coll Plant Protect, Key Lab Pesticide, Nanjing, Peoples R China 2.Van Andel Inst, Ctr Canc & Cell Biol, Program Struct Biol, Grand Rapids, MI 49503 USA 3.Northwestern Univ, Synchrotron Res Ctr, Life Sci Collaborat Access Team, Argonne, IL USA 4.Chinese Acad Sci, Ctr Struct & Funct Drug Targets, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Zhou, Yuxin,Zhou, X. Edward,Gong, Yuanping,et al. Structural basis of Fusarium myosin I inhibition by phenamacril[J]. PLOS PATHOGENS,2020,16(3):23. |
APA | Zhou, Yuxin.,Zhou, X. Edward.,Gong, Yuanping.,Zhu, Yuanye.,Cao, Xiaoman.,...&Zhang, Feng.(2020).Structural basis of Fusarium myosin I inhibition by phenamacril.PLOS PATHOGENS,16(3),23. |
MLA | Zhou, Yuxin,et al."Structural basis of Fusarium myosin I inhibition by phenamacril".PLOS PATHOGENS 16.3(2020):23. |
入库方式: OAI收割
来源:上海药物研究所
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