Inhibition of wheat embryo calcium-dependent protein kinase and avian myosin light chain kinase by flavonoids and related compounds

Avian Myosin light chain kinase (MLCK) is inhibited by a range of plant-derived Flavonoids. Maximal inhibition requires 2,3-unsaturation and polyhydroxylation of two of the three flavonoid rings. Phosphorylation of a synthetic Myosin light chain-related peptide by wheat embryo CA(2+)-dependent protein kinase (CDPK) is also inhibited by a range of Flavonoids but phosphorylation of histone preparation III-S by wheat CDPK is not inhibited by Flavonoids. The structural requirements for inhibition of wheat CDPK by Flavonoids are more stringent than for inhibition of avian MLCK. Potent flavonoid inhibitors of wheat CDPK are unsaturated in 2,3 position, have hydroxyl groups in positions 3' and 4' and an additional hydroxyl in the chromone ring. Flavonoid glycosylation or methylation can abolish inhibition. A number of Other naturally occurring plant phenolics including Chalcones and gossypol also inhibit avian MLCK and wheat CDPK. Gossypol binds to Calmodulin, abolishing CA(2+)-dependent enhancement of dansyl-calmodulin fluorescence.