Microbial Preparation of Guanosine 7-N-Oxide

KS-504a inhibited bovine brain calmodulin-dependent cyclic nucleotide phosphodieaterase (CaM-PDE) with an IC₅₀ value of 122 μm. The inhibition was reversed by a high concentration of calmodulin. Cal modulin-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 μm. The inhibition mechanism was competetive with respect to calmodulin and non-competetive to ATP.