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

Rasmus Wollenberg, Manuel H Taft, Sven Giese, Claudia Thiel, Zoltán Balázs, Henriette Giese, Dietmar Manstein, Teis Esben Sondergaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

1 Citation (Scopus)

Resumé

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 non-competitively inhibits ATP turnover, actin binding during ATP-turnover and motor activity of F. graminearum myosin-1. Phenamacril also inhibits the ATPase activity Fusarium avenaceum myosin-1 but has little or no inhibitory effect on the motor activity of Fusarium solani myosin-1, human myosin-1c, and Dictyostelium discoideum myosin isoforms 1B, 1E, and 2. Our findings indicate that phenamacril is a species-specific, non-competitive inhibitor of class I myosin in susceptible F.sp.
OriginalsprogEngelsk
TidsskriftJournal of Biological Chemistry
Vol/bind294
Udgave nummer4
Sider (fra-til)1328-1337
Antal sider10
ISSN0021-9258
DOI
StatusUdgivet - 25 jan. 2019

Citer dette

Wollenberg, Rasmus ; Taft, Manuel H ; Giese, Sven ; Thiel, Claudia ; Balázs, Zoltán ; Giese, Henriette ; Manstein, Dietmar ; Sondergaard, Teis Esben. / Phenamacril is a reversible and noncompetitive inhibitor of Fusarium class I myosin. I: Journal of Biological Chemistry. 2019 ; Bind 294, Nr. 4. s. 1328-1337.
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title = "Phenamacril is a reversible and noncompetitive inhibitor of Fusarium class I myosin",
abstract = "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 non-competitively inhibits ATP turnover, actin binding during ATP-turnover and motor activity of F. graminearum myosin-1. Phenamacril also inhibits the ATPase activity Fusarium avenaceum myosin-1 but has little or no inhibitory effect on the motor activity of Fusarium solani myosin-1, human myosin-1c, and Dictyostelium discoideum myosin isoforms 1B, 1E, and 2. Our findings indicate that phenamacril is a species-specific, non-competitive inhibitor of class I myosin in susceptible F.sp.",
author = "Rasmus Wollenberg and Taft, {Manuel H} and Sven Giese and Claudia Thiel and Zolt{\'a}n Bal{\'a}zs and Henriette Giese and Dietmar Manstein and Sondergaard, {Teis Esben}",
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Phenamacril is a reversible and noncompetitive inhibitor of Fusarium class I myosin. / Wollenberg, Rasmus; Taft, Manuel H; Giese, Sven; Thiel, Claudia; Balázs, Zoltán; Giese, Henriette; Manstein, Dietmar; Sondergaard, Teis Esben.

I: Journal of Biological Chemistry, Bind 294, Nr. 4, 25.01.2019, s. 1328-1337.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

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 (IC50 ~360 nM), reversibly, and non-competitively inhibits ATP turnover, actin binding during ATP-turnover and motor activity of F. graminearum myosin-1. Phenamacril also inhibits the ATPase activity Fusarium avenaceum myosin-1 but has little or no inhibitory effect on the motor activity of Fusarium solani myosin-1, human myosin-1c, and Dictyostelium discoideum myosin isoforms 1B, 1E, and 2. Our findings indicate that phenamacril is a species-specific, non-competitive inhibitor of class I myosin in susceptible F.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 (IC50 ~360 nM), reversibly, and non-competitively inhibits ATP turnover, actin binding during ATP-turnover and motor activity of F. graminearum myosin-1. Phenamacril also inhibits the ATPase activity Fusarium avenaceum myosin-1 but has little or no inhibitory effect on the motor activity of Fusarium solani myosin-1, human myosin-1c, and Dictyostelium discoideum myosin isoforms 1B, 1E, and 2. Our findings indicate that phenamacril is a species-specific, non-competitive inhibitor of class I myosin in susceptible F.sp.

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U2 - 10.1074/jbc.RA118.005408

DO - 10.1074/jbc.RA118.005408

M3 - Journal article

VL - 294

SP - 1328

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JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

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