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- Title
Structural basis of Fusarium myosin I inhibition by phenamacril.
- Authors
Zhou, Yuxin; Zhou, X. Edward; Gong, Yuanping; Zhu, Yuanye; Cao, Xiaoman; Brunzelle, Joseph S.; Xu, H. Eric; Zhou, Mingguo; Melcher, Karsten; Zhang, Feng
- Abstract
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.
- Subjects
SPECIES specificity; FUSARIUM; STRUCTURAL failures; FUNGICIDES; PHYTOPATHOGENIC microorganisms; MYOSIN; BARLEY
- Publication
PLoS Pathogens, 2020, Vol 16, Issue 3, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1008323