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针对 Fks1 蛋白的新型抗真菌药物发现。

Targeting Fks1 proteins for novel antifungal drug discovery.

机构信息

National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025, PR China; BMLT, Markham College of Commerce, Vinoba Bhave University, Hazaribagh, Jharkhand 825301, India.

School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, PR China.

出版信息

Trends Pharmacol Sci. 2024 Apr;45(4):366-384. doi: 10.1016/j.tips.2024.02.007. Epub 2024 Mar 15.

Abstract

Fungal infections are a major threat to human health. The limited availability of antifungal drugs, the emergence of drug resistance, and a growing susceptible population highlight the critical need for novel antifungal agents. The enzymes involved in fungal cell wall synthesis offer potential targets for antifungal drug development. Recent studies have enhanced our focus on the enzyme Fks1, which synthesizes β-1,3-glucan, a critical component of the cell wall. These studies provide a deeper understanding of Fks1's function in cell wall biosynthesis, pathogenicity, structural biology, evolutionary conservation across fungi, and interaction with current antifungal drugs. Here, we discuss the role of Fks1 in the survival and adaptation of fungi, guided by insights from evolutionary and structural analyses. Furthermore, we delve into the dynamics of Fks1 modulation with novel antifungal strategies and assess its potential as an antifungal drug target.

摘要

真菌感染是人类健康的主要威胁。抗真菌药物的供应有限、耐药性的出现以及易感人群的不断增加,突出表明我们迫切需要新型抗真菌药物。参与真菌细胞壁合成的酶为抗真菌药物的开发提供了潜在的靶点。最近的研究使我们更加关注合成β-1,3-葡聚糖的酶 Fks1,葡聚糖是细胞壁的关键组成部分。这些研究提供了对 Fks1 在细胞壁生物合成、致病性、结构生物学、真菌间的进化保守性以及与现有抗真菌药物相互作用中的功能的更深入了解。在这里,我们根据进化和结构分析的见解,讨论 Fks1 在真菌生存和适应中的作用。此外,我们深入研究了新型抗真菌策略对 Fks1 调节的动态,并评估了其作为抗真菌药物靶点的潜力。

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