TPS1 drug design for rice blast disease in magnaporthe oryzae
نویسندگان
چکیده
Magnaporthe oryzae (M. oryzae) is a fungal pathogen and the causal agent of rice blast disease. Previous lipidomics analysis of M. oryzae demonstrated that trehalose, a carbohydrate common to various fungi and algae, is thought to be involved in the possible conversion of glycogen into triacylglycerides for energy, an important step in the pathogenesis of M. oryzae. A key enzyme responsible for trehalose synthesis is trehalose-6-phosphate synthase 1 (Tps1). Therefore, we modeled the structure of Tps1 and sought to screen a chemical database in silico for possible inhibitors of the enzyme. Based on homologous alignment and sequence analysis, we first modeled the structure of Tps1 to determine the potential active site of the enzyme and its conformation. Using this model, we then undertook a docking study to determine the potential interaction that would manifest between Tsp1 and potential chemical inhibitors. Of the 400,000 chemicals screened in the Molecular Libraries Small Molecule Repository, we identified 45 potential candidates. The best candidate (Compound 24789937) was chosen and subjected to various structural optimization techniques to improve the suitability of the potential chemical inhibitors at the docking site of Tps1. From these modified versions of Compound 24789937, one lead compound (Lead 25) was shown to have the best binding affinity to Tps1 and good water solubility as compared with the ideal template compound and the other 44 potential candidates. Molecular dynamics simulation further confirmed the strength of the Tps1-Lead 25 complex and indicated the potential for Lead 25 to be used as an inhibitor of Tps1 in the control of M. oryzae-mediated rice blast disease.
منابع مشابه
Glycogen Metabolic Genes Are Involved in Trehalose-6-Phosphate Synthase-Mediated Regulation of Pathogenicity by the Rice Blast Fungus Magnaporthe oryzae
The filamentous fungus Magnaporthe oryzae is the causal agent of rice blast disease. Here we show that glycogen metabolic genes play an important role in plant infection by M. oryzae. Targeted deletion of AGL1 and GPH1, which encode amyloglucosidase and glycogen phosphorylase, respectively, prevented mobilisation of glycogen stores during appressorium development and caused a significant reduct...
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An NADPH-dependent genetic switch regulates plant infection by the rice blast fungus.
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متن کاملThe Sugar Sensor, Trehalose-6-Phosphate Synthase (Tps1), Regulates Primary and Secondary Metabolism during Infection by the Rice Blast Fungus: Will Magnaporthe oryzaeâ•Žs â•œSweet Toothâ•š become Its â•œAchillesâ•Ž Heelâ•š?
The Sugar Sensor, Trehalose-6-Phosphate Synthase (Tps1), Regulates Primary and Secondary Metabolism during Infection by the Rice Blast Fungus: Will Magnaporthe oryzae's " Sweet Tooth " become Its " Achilles' Heel " ?" (2011). Fungal Molecular Plant-Microbe Interactions. Paper 6. disparate cellular activities? To address this question, this review discusses our current understanding of tre-halos...
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