Dual-Specificity Inhibitor Targets Enzymes of the Trehalose Biosynthesis Pathway.
J Agric Food Chem
; 72(1): 209-218, 2024 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-38128269
ABSTRACT
To reduce the risk of resistance development, a novel fungicide with dual specificity is demanded. Trehalose is absent in animals, and its synthases, trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP), are safe fungicide targets. Here, we report the discovery of a dual-specificity inhibitor of MoTps1 (Magnaporthe oryzae Tps1, TPS) and MoTps2 (M. oryzae Tps2, TPP). The inhibitor, named A1-4, was obtained from a virtual screening and subsequent surface plasmon resonance screening. In in vitro assays, A1-4 interacts with MoTps1 and MoTps2-TPP (MoTps2 TPP domain) and inhibits their enzyme activities. In biological activity assays, A1-4 not only inhibits the virulence of M. oryzae on host but also causes aggregation of conidia cytosol, which is a characteristic phenotype of MoTps2. Furthermore, hydrogen/deuterium exchange mass spectrometry assays support the notion that A1-4 binds to the substrate pockets of TPS and TPP. Collectively, A1-4 is a promising hit compound for the development of safe fungicide with dual-target specificity.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Trealose
/
Fungicidas Industriais
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article