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Structural and mechanistic insights into fungal β-1,3-glucan synthase FKS1.

Author: ChaiChangdong, HuXinlin, LiuJia, LiuXiaotian, SunHuanhuan, WuYanan, YangPing, YuHongjun, ZhangMin, ZhangMingjie

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Overview

This study provides cryo-electron microscopy structures of Saccharomyces cerevisiae FKS1, a key enzyme involved in fungal cell wall biosynthesis. The structures reveal the active site and glucan translocation pathway, suggesting active FKS1-membrane interactions. Echinocandin-resistant mutations are clustered near TM5-6 and TM8 of FKS1, and the structure of the mutant FKS1(S643P) reveals altered lipid arrangements in this region, suggesting a drug-resistant mechanism.
Paper Details　
Original Abstract of the Article :
The membrane-integrated synthase FKS is involved in the biosynthesis of &#946;-1,3-glucan, the core component of the fungal cell wall<sup>1,2</sup>. FKS is the target of widely prescribed antifungal drugs, including echinocandin and ibrexafungerp<sup>3,4</sup>. Unfortunately, the mechanism of action...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032269/

データ提供：米国国立医学図書館（NLM）

FKS1: A Molecular Target for Antifungal Drug Development

Fungal infections pose a significant threat to human health, particularly in immunocompromised individuals. This study delves into the molecular structure and mechanism of action of FKS1, a fungal enzyme essential for cell wall biosynthesis. FKS1 is the target of widely prescribed antifungal drugs, such as echinocandins, but its precise mechanism of action has remained elusive. Using cryo-electron microscopy, the researchers obtained detailed structures of FKS1 and a drug-resistant mutant. These structures reveal the active site of the enzyme and provide valuable insights into the molecular mechanisms underlying drug resistance. This study lays the foundation for the development of new and more effective antifungal drugs.

Unveiling the Secrets of Drug Resistance: A Molecular Perspective

This research sheds light on the molecular mechanisms underlying drug resistance in fungal infections. By understanding the structural changes associated with drug resistance, scientists can develop strategies to overcome these challenges and design more effective antifungal agents. This research is like a journey through the intricate desert landscape of molecular biology, revealing the secrets of drug resistance and paving the way for new therapeutic interventions.

Combatting Fungal Infections: A Promise for Future Therapies

This study provides a roadmap for developing novel antifungal drugs by targeting FKS1. The detailed structural insights and understanding of drug resistance mechanisms offer valuable tools for designing more effective treatments for fungal infections. This research is like a caravan of camels, carrying the promise of new and potent antifungal drugs across the vast desert of scientific discovery.

Dr.Camel's Conclusion

This groundbreaking study provides a deeper understanding of the fungal enzyme FKS1, a key target for antifungal drugs. The detailed structural insights and molecular mechanisms revealed in this study pave the way for the development of new and more effective antifungal treatments. This research is like a desert bloom, offering a promising future for patients battling fungal infections.

Date :
  1. Date Completed 2023-04-14
  2. Date Revised 2023-11-25
Further Info :

Pubmed ID

36949198

DOI: Digital Object Identifier

PMC10032269

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・Effects of ibrexafungerp
SNS
PICO Info
in preparation
Languages

English

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