Inhibition of calmodulin activity by insect venom peptides.

Several peptides found in insect venom, including melittin, apamin and mastoparan, inhibited the activity of calmodulin-stimulated phosphodiesterase at concentrations that had no appreciable effect on basal phosphodiesterase activity; the Ki value of melittin for inhibiting calmodulin activity was 30 nM. Acetylation of the peptides reduced their inhibitory effect on calmodulin, suggesting that a net positive charge was an important determinant of anti-calmodulin activity. An examination of other structural features of these peptides suggested that the most potent inhibitors of calmodulin had an alpha-helical conformation. Equilibrium dialysis experiments showed that melittin inhibited the calcium-dependent binding of 3H-chlorpromazine to calmodulin (IC50 0.9 microM); kinetic analyses of these data indicated that this inhibition was non-competitive, suggesting that melittin and chlorpromazine act at different sites on calmodulin. Since calmodulin regulates a number of processes that these peptides inhibit, our results raise the possibility that the inhibition of calmodulin activity by these insect venom peptides may explain some of their biochemical or toxicological effects.