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. 2009 Apr;15(4):560–575. doi: 10.1261/rna.1416709

FIGURE 8.

FIGURE 8.

Plausible mechanisms for the reversible cleavage/ligation by the hairpin ribozyme consistent with the active site dynamics observed during MD. (A) Mechanism in which protonation of A38 is required to drive the active site toward the catalytic geometry and the protonated A38H+ acts as the general acid, while A9, A10, a water, or a nonbridging oxygen could serve as the base in the cleavage reaction. (B) Mechanism in which A38 acts as both general base and acid by shuttling a proton (gray sphere) directly from the 2′-OH of A-1 to the 5′-oxygen of G+1 for the cleavage reaction. In both mechanistic proposals G8, A10, A38, and water 5 stabilize the negative charge accumulated in the transition state. (C) Mechanism proposed for the protein-based serine-carboxyl peptidase kumamolisin-As (Wlodawer et al. 2004; Xu et al. 2007), analogous to the mechanism in panel B. A glutamate side chain with acidic solution pK a (4.3) acts as both general base and acid by shuttling a proton directly from the serine nucleophile with solution pK a of (∼13) to the leaving group during formation of the acylated enzyme.