Harmine is an ATP-competitive inhibitor for dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A)

► Harmine inhibits DYRK1A by competing against ATP. ► The V306A mutation in the ATP-binding pocket renders partial harmine resistance to DYRK1A. ► DYRK1A V306A mutant is fully functional in the presence of physiological concentrations of ATP. ► A model of harmine and DYRK1A interactions is proposed.