Figure 1. Schematic illustration of the VS ribozyme catalytic reaction.

The ribozyme catalyzes site-specific phosphodiester cleavage by using a guanine, G638, and an adenine, A756, as a general base and acid, respectively. The key catalytic strategies employed by ribozymes²³ are highlighted: α, acquirement of in-line nucleophilic attack (blue), β neutralization of negative charge on NPOs (green), γ deprotonation of the 2’-hydroxyl group to activate the nucleophile (red), and δ neutralization of negative charge on the 5’O leaving group (purple).