Identification of compounds exhibiting inhibitory activity toward the Pseudomonas tolaasii toxin tolaasin I using in silico docking calculations, NMR binding assays, and in vitro hemolytic activity assays.
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.
Lee
Younggiu
Y
Division of Bioscience and Biotechnology, BMIC, RCD, Konkuk University, Seoul 143-701, Republic of Korea.
Woo
Yoonkyung
Y
Lee
Soohyun
S
Kang
Kyungrai
K
Yong
Yeonjoong
Y
Kim
Jae Kyung
JK
Kim
Kwang Pyo
KP
Kim
Min-Hee
MH
Kim
Young-Kee
YK
Lim
Yoongho
Y
D000363:Agaricales / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019295:Computational Biology / Q000379:methods; D047630:Depsipeptides / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006461:Hemolysis; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011549:Pseudomonas / Q000378:metabolism*
D001426:Bacterial Proteins; D047630:Depsipeptides; D008024:Ligands; D010455:Peptides; C067241:tolaasin protein, Pseudomonas tolaasii