K-254-I (Genistein), a New Inhibitor of Ca2+ and Calmodulin-Dependent Cyclic Nucleotide Phosphodiesterase from Streptosporangium vulgare

A new calmodulin antagonist, genistein, was isolated from the culture broth of Strepto-sporangium vulgare K-254. The spectral data of K-254-I indicated that the compound was identical with genistein, 4/,5,7-trihydroxyisoflavone. Genistein inhibited the Ca2+/calmodulin-depen- dent activity of cyclic nucleotide phosphodiesterase from bovine brain (IC50 = 20 μΜ) without appreciably affecting its basal activity. The inhibitory activity of genistein was antagonized by higher concentrations of calmodulin. Although phosphatidylserine did not reverse the inhibition of calmodulin, genistein inhibited the phospholipid-sensitive, Ca2 +-dependent protein kinase (protein kinase C) from bovine brain (IC50 = 35.3 μΜ). The activity of cAMP-dependent protein kinase was not affected by 700 μΜ of genistein.