biostudies-literatureWollenberg RDTeknologi og Produktion, Det Frie ForskningsrådVolkswagen Foundation1328-1337https://www.ebi.ac.uk/biostudies/studies/S-EPMC6349130biostudies-literatureUnknown294(4)The cyanoacrylate compound phenamacril (also known as JS399-19) is a recently identified fungicide that exerts its antifungal effect on susceptible <i>Fusarium</i> 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 <i>Fusarium graminearum</i>, phenamacril-resistant <i>Fusarium</i> species, and the mycetozoan model organism <i>Dictyostelium discoideum</i> Our results show that phenamacril potently (IC₅₀ ∼360 nm), reversibly, and noncompetitively inhibits ATP turnover, actin binding during ATP turnover, and motor activity of <i>F. graminearum</i> myosin-1. Phenamacril also inhibits the ATPase activity of <i>Fusarium avenaceum</i> myosin-1 but has little or no inhibitory effect on the motor activity of <i>Fusarium solani</i> myosin-1, human myosin-1c, and <i>D. discoideum</i> myosin isoforms 1B, 1E, and 2. Our findings indicate that phenamacril is a species-specific, noncompetitive inhibitor of class I myosin in susceptible <i>Fusarium</i> sp.The Journal of biological chemistryPhenamacril is a reversible and noncompetitive inhibitor of <i>Fusarium</i> class I myosin.PMC63491304005–00204BVWZN3012Wollenberg RDGiese HSondergaard TEBalazs ZTaft MHGiese SThiel CManstein DJfalsePhenamacril is a reversible and noncompetitive inhibitor of <i>Fusarium</i> class I myosin.The cyanoacrylate compound phenamacril (also known as JS399-19) is a recently identified fungicide that exerts its antifungal effect on susceptible <i>Fusarium</i> 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 <i>Fusarium graminearum</i>, phenamacril-resistant <i>Fusarium</i> species, and the mycetozoan model organism <i>Dictyostelium discoideum</i> Our results show that phenamacril potently (IC₅₀ ∼360 nm), reversibly, and noncompetitively inhibits ATP turnover, actin binding during ATP turnover, and motor activity of <i>F. graminearum</i> myosin-1. Phenamacril also inhibits the ATPase activity of <i>Fusarium avenaceum</i> myosin-1 but has little or no inhibitory effect on the motor activity of <i>Fusarium solani</i> myosin-1, human myosin-1c, and <i>D. discoideum</i> myosin isoforms 1B, 1E, and 2. Our findings indicate that phenamacril is a species-specific, noncompetitive inhibitor of class I myosin in susceptible <i>Fusarium</i> sp.2019-01-01T00:00:00Z2019 Jan2024-10-18T20:38:28.927Z2024-10-18T20:38:28.927ZS-EPMC63491303050422210.1074/jbc.ra118.00540810.1074/jbc.RA118.005408