TY - JOUR
T1 - Phenamacril is a reversible and noncompetitive inhibitor of Fusarium class I myosin
AU - Wollenberg, Rasmus
AU - Taft, Manuel H
AU - Giese, Sven
AU - Thiel, Claudia
AU - Balázs, Zoltán
AU - Giese, Henriette
AU - Manstein, Dietmar
AU - Sondergaard, Teis Esben
N1 - © 2019 Wollenberg et al.
PY - 2019/1/25
Y1 - 2019/1/25
N2 - 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 (IC
50 ∼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.
AB - 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 (IC
50 ∼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.
KW - Fungicides, Industrial/pharmacology
KW - Fusarium/drug effects
KW - Gene Expression Regulation, Fungal/drug effects
KW - Myosin Type I/antagonists & inhibitors
KW - Protein Conformation
KW - Species Specificity
UR - http://www.scopus.com/inward/record.url?scp=85060648022&partnerID=8YFLogxK
U2 - 10.1074/jbc.RA118.005408
DO - 10.1074/jbc.RA118.005408
M3 - Journal article
C2 - 30504222
AN - SCOPUS:85060648022
SN - 0021-9258
VL - 294
SP - 1328
EP - 1337
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 4
ER -