Fig. 5. Mebendazole (MBZ) effectively interacts with the colchicine-binding site of
β-tubulin. (A, B) β-tubulin protein levels in CML cells were detected using CETSA and the quantitative data were shown on the right. The values are the mean ± SD of three independent experiments. (C) Molecular structures of colchicine. (D) The binding pose of colchicine (orange) with tubulin in the crystal structure (PDB ID: 4O2B) and predicted orientation of colchicine (green) in silico docking analysis. (E) The predicted binding orientation and interactions of MBZ (red) in the α/β-tubulin heterodimer (purple, PDB ID: 4O2B) with a binding affinity of −10.1 kcal/mol. Key amino acid residues are visualized in sticks. Hydrogen bonds (green), and hydrophobic interactions (pink) are indicated as dashed lines. (F) The levels of active β-tubulin and EBI: β-tubulin adduct were detected by CETSA and western blot. CML, chronic myeloid leukemia; CETSA, cellular thermal shift assay; EBI, N, N′-ethylenebis(iodoacetamide); DMSO, dimethyl sulfoxide.
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