Calmodulin antagonistic action of KS-504a, a novel metabolite of the fungus Mollisia ventosa.

KS-504a inhibited bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase (CaM-PDE) with an IC50 value of 122 microM. The inhibition was reversed by a high concentration of calmodulin. Calmodulin-independent activities of the enzyme were not affected by the compound at the same concentration ranges. Ca2(+)-dependent interaction of the compounds with calmodulin was shown using hydrophobic fluorescence probes. These data indicated that the compound exerted its effects on CaM-PDE by interacting with calmodulin. KS-504a also inhibited other calmodulin-dependent enzymes at different concentration ranges; myosin light chain kinase was inhibited at the lowest concentrations with an IC50 value of 6.3 microM. The inhibition mechanism was competitive with respect to calmodulin and non-competitive to ATP.