FIGURE 1.

The four strategies that shape discussions of catalysis by small nucleolytic ribozymes (Emilsson et al. 2003): (α) in-line fitness of the 2-OH′ nucleophile, (β) electrostatic stabilization/protonation of the NPOs in the transition state, (γ) deprotonation (activation) of the 2′-OH nucleophile (e.g., by a general base), and (δ) stabilization/protonation of the 5′-O leaving group (e.g., by a general acid). Recently, an ontology has been introduced that extends this framework for more precise discussion of mechanisms of RNA-cleaving enzymes by decomposing the β, γ, and δ strategies into primary (1°), secondary (2°), and tertiary (3°) contributions (Bevilacqua et al. 2019).