{"title":"揭示 F. graminearum 对 Phenamacril 的抗性机理:对 FgMyoI 中 C423A 突变的计算和实验见解。","authors":"Yiqiong Bao, Fangying Jia, Yun Lin, Guohong Song, Mengrong Li, Ran Xu, Hancheng Wang, Feng Zhang, Jingjing Guo","doi":"10.1021/acs.jafc.4c03467","DOIUrl":null,"url":null,"abstract":"<p><p>Phenamacril (PHA) is a highly selective fungicide for controlling fusarium head blight (FHB) mainly caused by <i>F. graminearum</i> and <i>F. asiaticum</i>. However, the C423A mutation in myosin I of <i>F. graminearum</i> (FgMyoI) leads to natural resistance to PHA. Here, based on the computational approaches and biochemical validation, we elucidate the atomic-level mechanism behind the natural resistance of <i>F. graminearum</i> to the fungicide PHA due to the C423A mutation in FgMyoI. The mutation leads to a rearrangement of pocket residues, resulting in increased size and flexibility of the binding pocket, which impairs the stable binding of PHA. MST experiments confirm that the mutant protein FgMyoI<sup>C423A</sup> exhibits significantly reduced affinity for PHA compared to wild-type FgMyoI and the nonresistant C423K mutant. This decreased binding affinity likely underlies the development of PHA resistance in <i>F. graminearum</i>. Conversely, the nonresistant C423K mutant retains sensitivity to PHA due to the introduction of a strong hydrogen bond donor, which facilitates stable binding of PHA in the pocket. These findings shed light on the molecular basis of PHA resistance and provide new directions for the creation of new myosin inhibitors.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unveiling the Mechanism of Phenamacril Resistance in <i>F. graminearum</i>: Computational and Experimental Insights into the C423A Mutation in FgMyoI.\",\"authors\":\"Yiqiong Bao, Fangying Jia, Yun Lin, Guohong Song, Mengrong Li, Ran Xu, Hancheng Wang, Feng Zhang, Jingjing Guo\",\"doi\":\"10.1021/acs.jafc.4c03467\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Phenamacril (PHA) is a highly selective fungicide for controlling fusarium head blight (FHB) mainly caused by <i>F. graminearum</i> and <i>F. asiaticum</i>. However, the C423A mutation in myosin I of <i>F. graminearum</i> (FgMyoI) leads to natural resistance to PHA. Here, based on the computational approaches and biochemical validation, we elucidate the atomic-level mechanism behind the natural resistance of <i>F. graminearum</i> to the fungicide PHA due to the C423A mutation in FgMyoI. The mutation leads to a rearrangement of pocket residues, resulting in increased size and flexibility of the binding pocket, which impairs the stable binding of PHA. MST experiments confirm that the mutant protein FgMyoI<sup>C423A</sup> exhibits significantly reduced affinity for PHA compared to wild-type FgMyoI and the nonresistant C423K mutant. This decreased binding affinity likely underlies the development of PHA resistance in <i>F. graminearum</i>. Conversely, the nonresistant C423K mutant retains sensitivity to PHA due to the introduction of a strong hydrogen bond donor, which facilitates stable binding of PHA in the pocket. These findings shed light on the molecular basis of PHA resistance and provide new directions for the creation of new myosin inhibitors.</p>\",\"PeriodicalId\":41,\"journal\":{\"name\":\"Journal of Agricultural and Food Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Agricultural and Food Chemistry\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jafc.4c03467\",\"RegionNum\":1,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"AGRICULTURE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Agricultural and Food Chemistry","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1021/acs.jafc.4c03467","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"AGRICULTURE, MULTIDISCIPLINARY","Score":null,"Total":0}
Unveiling the Mechanism of Phenamacril Resistance in F. graminearum: Computational and Experimental Insights into the C423A Mutation in FgMyoI.
Phenamacril (PHA) is a highly selective fungicide for controlling fusarium head blight (FHB) mainly caused by F. graminearum and F. asiaticum. However, the C423A mutation in myosin I of F. graminearum (FgMyoI) leads to natural resistance to PHA. Here, based on the computational approaches and biochemical validation, we elucidate the atomic-level mechanism behind the natural resistance of F. graminearum to the fungicide PHA due to the C423A mutation in FgMyoI. The mutation leads to a rearrangement of pocket residues, resulting in increased size and flexibility of the binding pocket, which impairs the stable binding of PHA. MST experiments confirm that the mutant protein FgMyoIC423A exhibits significantly reduced affinity for PHA compared to wild-type FgMyoI and the nonresistant C423K mutant. This decreased binding affinity likely underlies the development of PHA resistance in F. graminearum. Conversely, the nonresistant C423K mutant retains sensitivity to PHA due to the introduction of a strong hydrogen bond donor, which facilitates stable binding of PHA in the pocket. These findings shed light on the molecular basis of PHA resistance and provide new directions for the creation of new myosin inhibitors.
期刊介绍:
The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.