SNase reaction mechanism

FIGURE 8.3. The energetics of an hypothetical reference reaction that corresponds to the assumed mechanism of SNase but occurs in a solvent cage. 

Extensive calculations of the reaction free energy profile for the postulated mechanism of SNase (Aqvist and Warshel, 1989 1990) achieved quantitative agreement between calculated and observed free energy barriers. It was concluded that the general-base mechanism itself is not a sufficiently effective way of generating the hydroxyl ion and the Ca2t ion is essential for stabilisation. 

The stereochemical consequences of the reactions catalyzed by these two phosphodiesterases are the opposite of those determined for the reactions catalyzed by SNase and DNase I. The structural and mechanistic divergence already noted for the two phosphodiesterases, which require Ca for activity and probably involve general base-assisted attack of water on the substrate, is expanded on by the finding that the phosphodiesterases from snake venom and spleen utilize mechanisms that have retention as their stereochemical outcomes. Clearly, the stereochemical and structural studies of phosphodiesterases reported to date reveal mechanistic complexity that contrasts with the stereochemical (and mechanistic) uniformity that has been discovered for all of the kinases studied to date. The diversity in the phosphodiesterases is perhaps even more surprising when it is realized that the substrates for all of the enzymes that have been stereochemi-... 

Figure 5.3 Free energy diagram based on experimental kinetic data (see text for references) for the reference solution reactions corresponding to the mechanism proposed for SNase.

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