Figure 6.

Calculated pH dependence of the cleavage reaction of the VS ribozyme as a function of base pK_A, assuming general acid–base catalysis. The fractions of protonated acid f_A, unprotonated base f_B and their product f_A·f_B have been calculated and plotted as a function of pH, following the approach of Bevilacqua (2003). The shaded sections are the regions of pH not accessible to experimental study. Reaction rate should be proportional to the fraction of ribozyme in the appropriate state of protonation, that is, f_A·f_B. Note that in these graphs, f_A and f_B are plotted on a log₁₀ scale (left), whereas f_A·f_B is plotted on a linear scale (right). (A) Plot for pK_A values of 5.5 and 9 for the acid and base, respectively. This might correspond to the natural ribozyme, assuming that the acid is an adenine with an elevated pK_A and the base is a guanine with a slightly reduced pK_A. The predicted reaction rate profile is a broad bell shape, with a maximum close to neutrality. (B) Plot for pK_A values of 5.5 and 5 for the acid and base, respectively. This situation could emerge if the guanine were replaced by a nucleobase of significantly lower pK_A (e.g. adenine or DAP). The reaction rate is predicted to exhibit a marked increase at low pH, with a maximum that is just detectable for these values.