Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents
Figure 2
Ribozyme mechanism. A schematic reperesentation is shown with a simplified accessible region in a target mRNA with a cleavable hhRz NUH motif, (GUC). The hhRz, drawn in an open enzymatically patent state, binds to the accessible target region by Watson Crick base pairing. Annealing precisely aligns the phosphodiester bond of the H residue (C here) with the enzymatic core of the catalytic RNA. The annealing reaction has an equilibrium specified by the ratio of rates and . Chemical cleavage () occurs to yield two products which remain bound to the AS flanks of the hhRz. Each product leaves with its own characteristic equilibrium determined by the strength of binding to the hhRz AS flanks. Product dissociation permits the enzyme to collide with another substrate and initiate subsequent rounds of catalysis as a Michaelis-Menten enzyme to achieve catalytic target turnover characterized by .
