In the sense that they activate the 25" Ca*+-adenosine-5'-triphosphatase, inhibit the 25" Ca*+inosine-5'-triphosphatase, and inhibit the 0' activity of both nucleosidetriphosphatases, dioxane and hydrogen peroxide are true "modifiers" of myosin nucleosidetriphosphatase. Modification by peroxide, as by p-mercuribenzoate, clearly involves reaction of certain myosin sulfhydryl groups, but no compelling evidence for sulfhydryl involvement was found in modification by dioxane, and there was found some direct evidence against sulfhydryl involvement in modification by 2,Cdinitrophenol. On the other hand, the groups on the myosin molecule directly responsible for either activating or inhibiting phases of "modification" are probably the same for all modifiers. This hypothesis, expressed quantitatively in a stochastic model, was afbmatively tested in the case of p-mercuribenzoate and 2,4-dinitrophenol. It was found incidentally that histidine protects against modification which involves oxidation because histidine itself is easily oxidized in a reaction involving its amino group.We are concerned in this paper with interpreting experiments in which the nucleosidetriphosphatase activity of CaZ+-myosin is modified by various reagents. Such an objective presumes that the activity of unmodified enzyme is understood, and this is not really the case. However, as a result of the work of many laboratories, there is a hypothesis about unmodified and modified myosin catalysis into which many observations seem to fit, and it is useful to state this hypothesis at the outset and in some degree to justify it a posteriori.A Hypothesis about Myosin Nucleosidetriphosphatase. -In most experiments with substrate-saturated and Ca*+-saturated myosin, the substrate is ATP, the temperature is ea. 25', and the p H is near neutral. These conditions have come to define the "normal" or reference behavior of the enzyme, and one can discuss consequences of changing conditions; for example, at 25" a partial titration of the sulfhydryl content activates ATPase and inhibits ITPase,' but at 0" the same titration inhibits both. We (see Gilmour, 1960;Morales and Hotta, 1960) have felt it helpful to focus on more general properties of the enzyme and of the reagents which affect it. In our terms, the crucial properties of myosin catalysis are as follows (see also Figs. 1 and 2).
