Role of Calmodulin Inhibition in the Mode of Action of Ophiobolin A

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Abstract
Calmodulin was isolated from the root of Zea mays. It activates the bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase and has electrophoretic mobility very similar to that of bovine brain calmodulin. Ophiobolin A, a fungal toxin [isolated from Helminthosporium maydis], interacts with the maize calmodulin. The interaction is not reversed by dilution or denaturation in SDS [sodium dodecyl sulfate] and results in the loss of ability of the calmodulin to activate the phosphodiesterase. The inhibition is much faster in the presence than in the absence of Ca2+. The electrophoretic mobility of ophiobolin A-treated calmodulin is less than that of untreated calmodulin. Several similarities are found between the inhibition of maize calmodulin by ophiobilin A in vitro and the effects of ophiobolin A on excised roots. Both are irreversible and time-dependent. The concentration of ophiobolin A for half-maximal inhibition of calmodulin in the phosphodiesterase assay is similar to that for phototoxicity. In both cases ophiobolin A derivatives behave similarly, i.e., 18-bromo-19-methoxyophiobolin A is as potent as ophiobolin A, while 3-anhydro-ophiobolin A and 6-epi-ophiobolin A are less potent. A smaller amount of active calmodulin was measured in the extract from ophiobolin A-treated roots than in those from untreated roots. Calmodulin apparently is a target molecule in the root for the toxicity of ophiobolin A.