Analysis of binding mode of vibsanin A with protein kinase C C1 domains: An experimental and molecular dynamics simulation study

•Structure–protein kinase C (PKC) binding activity study of vibsanins was conducted.•The epoxy group in vibsanin A may play a role in binding to protein kinase C (PKC).•Molecular dynamics simulation of PKC C1 domain/vibsanin A/membrane was performed.•Ester group of vibsanin A may form CH–O hydrogen bonds with the protein. Vibsanin A (VibA), isolated from Viburnum odoratissimum, binds to and activates protein kinase C (PKC) isozymes to induce leukemia cell differentiation. VibA is a promising seed compound for developing PKC-activating drugs because it exhibits anti-proinflammatory activity, atypical to PKC activators. However, the role of hydrogen bond-forming functional groups and the precise binding mode with C1 domains in PKC isozymes remains unknown. In this study, we evaluated the PKC-binding ability of natural vibsanins and synthetic 1′-desoxo-VibA (1) and performed molecular dynamics simulation of membrane/C1 domain-bound VibA to predict the binding mode of VibA with C1 domains. Experimental and simulation results indicated that the ester group in VibA is involved in CH–O hydrogen bonds with PKC C1 domains. Alternatively, a growth-inhibition assay against leukemia cells revealed that the ester group of VibA negatively affects antiproliferative activity. [Display omitted]