Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights

Autor: Yue Zhou, Todd B. Reynolds
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Fungi, Vol 10, Iss 3, p 171 (2024)
Druh dokumentu: article
ISSN: 2309-608X
DOI: 10.3390/jof10030171
Popis: Life-threatening systemic fungal infections occur in immunocompromised patients at an alarming rate. Current antifungal therapies face challenges like drug resistance and patient toxicity, emphasizing the need for new treatments. Membrane-bound enzymes account for a large proportion of current and potential antifungal targets, especially ones that contribute to cell wall and cell membrane biosynthesis. Moreover, structural biology has led to a better understanding of the mechanisms by which these enzymes synthesize their products, as well as the mechanism of action for some antifungals. This review summarizes the structures of several current and potential membrane-bound antifungal targets involved in cell wall and cell membrane biosynthesis and their interactions with known inhibitors or drugs. The proposed mechanisms of action for some molecules, gleaned from detailed inhibitor–protein studeis, are also described, which aids in further rational drug design. Furthermore, some potential membrane-bound antifungal targets with known inhibitors that lack solved structures are discussed, as these might be good enzymes for future structure interrogation.
Databáze: Directory of Open Access Journals
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