Unraveling the molecular mechanism of FgGcn5 inhibition by phenazine-1-carboxamide: combined in silico and in vitro studies.

IF 3.8 1区农林科学 Q1 AGRONOMY Pest Management Science Pub Date : 2025-02-01 Epub Date: 2024-10-28 DOI:10.1002/ps.8496

Lei Li, Qing Luo, Shuai Yang, Hancheng Wang, Yuguang Mu, Jingjing Guo, Feng Zhang

{"title":"Unraveling the molecular mechanism of FgGcn5 inhibition by phenazine-1-carboxamide: combined in silico and in vitro studies.","authors":"Lei Li, Qing Luo, Shuai Yang, Hancheng Wang, Yuguang Mu, Jingjing Guo, Feng Zhang","doi":"10.1002/ps.8496","DOIUrl":null,"url":null,"abstract":"Background: Fusarium head blight (FHB), mainly caused by Fusarium graminearum (F. graminearum), remains a devastating disease worldwide. The histone acetyltransferase Gcn5 plays a crucial role in epigenetic regulation. Aberrant Gcn5 acetylation activity can result in serious impacts such as impaired growth and development in organisms. The secondary metabolite phenazine-1-carboxamide (PCN) inhibits F. graminearum by blocking the acetylation process of Gcn5 (FgGcn5), and is currently used to control FHB. However, the molecular basis of acetylation inhibition by PCN remains to be further explored.Results: Our molecular dynamics simulations revealed that PCN binds to the cleft in FgGcn5 where histone H3 is bound, with key amino acid residues including Leu96 (L96), Arg121 (R121), Phe133 (F133), Tyr169 (Y169), and Tyr201 (Y201), preventing FgGcn5 from binding to histone H3 and affecting histone H3 from being acetylated. Experimental validation of key amino acid mutations further confirmed the impact of these mutations on the interaction of FgGcn5 with PCN and histone H3 peptide.Conclusion: In summary, our study sheds light on the mechanism by which PCN inhibits the acetylation function of FgGcn5, providing a foundation for the development of drugs or fungicides targeting histone acetyltransferases. © 2024 Society of Chemical Industry.","PeriodicalId":218,"journal":{"name":"Pest Management Science","volume":" ","pages":"937-945"},"PeriodicalIF":3.8000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pest Management Science","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1002/ps.8496","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"AGRONOMY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Fusarium head blight (FHB), mainly caused by Fusarium graminearum (F. graminearum), remains a devastating disease worldwide. The histone acetyltransferase Gcn5 plays a crucial role in epigenetic regulation. Aberrant Gcn5 acetylation activity can result in serious impacts such as impaired growth and development in organisms. The secondary metabolite phenazine-1-carboxamide (PCN) inhibits F. graminearum by blocking the acetylation process of Gcn5 (FgGcn5), and is currently used to control FHB. However, the molecular basis of acetylation inhibition by PCN remains to be further explored.

Results: Our molecular dynamics simulations revealed that PCN binds to the cleft in FgGcn5 where histone H3 is bound, with key amino acid residues including Leu96 (L96), Arg121 (R121), Phe133 (F133), Tyr169 (Y169), and Tyr201 (Y201), preventing FgGcn5 from binding to histone H3 and affecting histone H3 from being acetylated. Experimental validation of key amino acid mutations further confirmed the impact of these mutations on the interaction of FgGcn5 with PCN and histone H3 peptide.

Conclusion: In summary, our study sheds light on the mechanism by which PCN inhibits the acetylation function of FgGcn5, providing a foundation for the development of drugs or fungicides targeting histone acetyltransferases. © 2024 Society of Chemical Industry.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

揭示吩嗪-1-甲酰胺抑制 FgGcn5 的分子机制：硅学和体外联合研究。

背景：镰刀菌头枯病（FHB）主要由禾谷镰刀菌（F. graminearum）引起，目前仍是一种全球性的毁灭性病害。组蛋白乙酰转移酶 Gcn5 在表观遗传调控中起着至关重要的作用。异常的 Gcn5 乙酰化活性会导致生物体生长和发育受损等严重影响。次级代谢物酚嗪-1-甲酰胺（PCN）通过阻断 Gcn5（FgGcn5）的乙酰化过程来抑制禾谷粉虱，目前被用于防治禾谷粉虱。然而，PCN 抑制乙酰化的分子基础仍有待进一步探索：我们的分子动力学模拟发现，PCN与FgGcn5中组蛋白H3结合的裂隙结合，关键氨基酸残基包括Leu96 (L96)、Arg121 (R121)、Phe133 (F133)、Tyr169 (Y169)和Tyr201 (Y201)，从而阻止FgGcn5与组蛋白H3结合，影响组蛋白H3乙酰化。关键氨基酸突变的实验验证进一步证实了这些突变对 FgGcn5 与 PCN 和组蛋白 H3 肽相互作用的影响：总之，我们的研究揭示了 PCN 抑制 FgGcn5 乙酰化功能的机制，为开发针对组蛋白乙酰转移酶的药物或杀菌剂奠定了基础。© 2024 化学工业协会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Pest Management Science 农林科学-昆虫学

CiteScore

7.90

自引率

9.80%

发文量

553

审稿时长

4.8 months

期刊介绍： Pest Management Science is the international journal of research and development in crop protection and pest control. Since its launch in 1970, the journal has become the premier forum for papers on the discovery, application, and impact on the environment of products and strategies designed for pest management. Published for SCI by John Wiley & Sons Ltd.