Phenamacril is a reversible and noncompetitive inhibitor of Fusarium class I myosin
Phenamacril is a reversible and noncompetitive inhibitor of Fusarium class I myosin
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DOI：
10.1074/jbc.ra118.005408
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发表时间：
2019-01-25
影响因子：
4.8
通讯作者：
Sondergaard, Teis E.
中科院分区：
文献类型：
--
作者：
Wollenberg, Rasmus D.;Taft, Manuel H.;Sondergaard, Teis E.
氰基丙烯酸酯化合物非那普利（也称为JS 399 -19）是最近鉴定的杀真菌剂，其通过抑制其肌球蛋白I类马达结构域的ATP酶活性而对易感镰刀菌属物种发挥其抗真菌作用。尽管对非那普利的抗真菌谱了解很多，但非那普利介导的抑制作用背后的确切机制仍有待解决。在这里，我们描述了phenamacril对纯化的肌球蛋白电机结构的模式植物病原体和phenamacril敏感的物种禾谷镰刀菌，phenamacril抗性镰刀菌物种，和mycetozoan模式生物Dictyosteelium discoideum的影响的表征。我们的研究结果表明，phenamacril有效（IC 50类似于360 nm），可逆，非竞争性抑制ATP周转，肌动蛋白结合ATP周转期间，和运动活动的F。禾谷小麦肌球蛋白-1。非那普利还抑制燕麦镰刀菌肌球蛋白-1的ATP酶活性，但对茄病镰刀菌肌球蛋白-1、人肌球蛋白-1c和D. discoideum肌球蛋白同种型1B、1 E和2。我们的研究结果表明，非那普利是一个物种特异性，非竞争性抑制剂的I类肌球蛋白在易感镰刀菌。
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 similar to 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.