Fig. 4: Identification of the kinase target and its binding site of a fungicide. | Nature Communications

Fig. 4: Identification of the kinase target and its binding site of a fungicide.

From: A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes

Fig. 4

a Chemical structure of the novel compound BAYE-004. b Inhibition of growth in Botrytis cinerea cells upon treatment with increasing concentrations of BAYE-004. c Dose–response curves showing relative intensities of the top two LiP-Quant peptides from Bcin06g02870, based on LiP-Quant score in the presence of increasing concentrations of BAYE-004. Bcin06g02870 is a serine/threonine kinase predicted to be casein kinase I. The extrapolated average EC50 for this protein is 6 nM. d Thermal stability of His-tagged Bcin06g02870 upon treatment with increasing concentrations of BAYE-004. Western blots and the corresponding quantification of the soluble fraction of Bcin06g02870 at 56 °C (n = 2). e Homology model of the structure of Bcin16g04330 kinase (from template PDBID: 3gzd, see Methods section). Red dot shows the center of mass of the LiP-Quant peptides (pink) for this protein. Magenta dots represent a 4 Å radius around the center of mass. It is positioned within the volume of the catalytic site (cyan), which is a common binding site of other kinase inhibitors. The volume of the catalytic site was calculated based on a model of a protein bound to a kinase inhibitor (PDBID: 3gzd). f LANCE Ultra kinase assay of CK-1 inhibition upon incubation with increasing concentrations of BAYE-004. Source data are provided as a Source Data file.

Back to article page