ABSTRACT
A toxin produced by Pseudomonas tolaasii, tolaasin, causes brown blotch disease in mushrooms. Tolaasin forms pores on the cellular membrane and destroys cell structure. Inhibiting the ability of tolaasin to form ion channels may be an effective method to protect against attack by tolaasin. However, it is first necessary to elucidate the three-dimensional structure of the ion channels formed by tolaasin. In this study, the structure of the tolaasin ion channel was determined in silico based on data obtained from nuclear magnetic resonance experiments.
Subject(s)
Bacterial Proteins/chemistry , Bacterial Toxins/chemistry , Depsipeptides/chemistry , Ion Channels/chemistry , Pseudomonas/metabolism , Amino Acid Sequence , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Depsipeptides/genetics , Depsipeptides/metabolism , Ion Channels/genetics , Ion Channels/metabolism , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Sequence Data , Pseudomonas/chemistry , Pseudomonas/geneticsABSTRACT
Compounds extracted from Platycodon grandiflorum were evaluated for an activation effect on nuclear factor-kappa B (NF-kappaB). In its active state, NF-kappaB turns on the expression of genes related to cell proliferation or death. NF-kappaB activators promote growth of neuron cells and can be used to control neurodegenerative diseases. The biological activity of P. grandiflorum extracts toward NF-kappaB had not yet been studied. Although the biological activity of several compounds extracted from P. grandiflorum was evaluated, only three exhibited any significant activation effect on NF-kappaB.
Subject(s)
NF-kappa B/biosynthesis , Plant Extracts/pharmacology , Platycodon , Transcriptional Activation/drug effects , Cell Line , Gene Expression/drug effects , Genes, Reporter/drug effects , Humans , NF-kappa B/genetics , Plant Extracts/isolation & purification , Plant Roots , Polyynes/isolation & purification , Polyynes/pharmacologyABSTRACT
Using in silico docking calculations, NMR analysis of target-ligand binding, and hemolytic activity assays, we searched a 30,000-compound library for an effective inhibitor of tolaasin I, a Pseudomonas tolaasii toxin that causes virulent infection in mushrooms. Of more than 30,000 compounds screened in silico, two compounds were selected. One of these compounds, sorbitololeic acid, bound to tolaasin I and inhibited its hemolytic activity in vitro. Therefore, sorbitololeic acid can be a potential inhibitor of tolaasin I.
