Phenamacril is a reversible and noncompetitive inhibitor of Fusarium class I myosin

The cyanoacrylate compound phenamacril (also known as JS399–19) is a recently identified fungicide that exerts its antifungal effect on susceptible Fusarium species by inhibiting the ATPase activity of their myosin class I motor domains. Although much is known about the antifungal spectrum of phenam...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2019-01, Vol.294 (4), p.1328-1337
Main Authors: Wollenberg, Rasmus D., Taft, Manuel H., Giese, Sven, Thiel, Claudia, Balázs, Zoltán, Giese, Henriette, Manstein, Dietmar J., Sondergaard, Teis E.
Format: Article
Language:English
Subjects:
allosteric regulation
ATPase
cytoskeleton
fungi
fungicide
Fungicides, Industrial - pharmacology
Fusarium - drug effects
Fusarium - growth & development
Fusarium - metabolism
Gene Expression Regulation, Fungal - drug effects
inhibition mechanism
inhibitor
Molecular Biophysics
motor protein
myosin
Myosin Type I - antagonists & inhibitors
phenamacril
Protein Conformation
Species Specificity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The cyanoacrylate compound phenamacril (also known as JS399–19) is a recently identified fungicide that exerts its antifungal effect on susceptible Fusarium species by inhibiting the ATPase activity of their myosin class I motor domains. Although much is known about the antifungal spectrum of phenamacril, the exact mechanism behind the phenamacril-mediated inhibition remains to be resolved. Here, we describe the characterization of the effect of phenamacril on purified myosin motor constructs from the model plant pathogen and phenamacril-susceptible species Fusarium graminearum, phenamacril-resistant Fusarium species, and the mycetozoan model organism Dictyostelium discoideum. Our results show that phenamacril potently (IC50 ∼360 nm), reversibly, and noncompetitively inhibits ATP turnover, actin binding during ATP turnover, and motor activity of F. graminearum myosin-1. Phenamacril also inhibits the ATPase activity of Fusarium avenaceum myosin-1 but has little or no inhibitory effect on the motor activity of Fusarium solani myosin-1, human myosin-1c, and D. discoideum myosin isoforms 1B, 1E, and 2. Our findings indicate that phenamacril is a species-specific, noncompetitive inhibitor of class I myosin in susceptible Fusarium sp.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.RA118.005408