Probable catalytic mechanisms, and a strong similarity between the VS and hairpin ribozymes. (A) Two catalytic mechanisms based on the participation of G638 and A756 in general acid–base catalysis. In one possibility (upper), the guanine acts as the general base deprotonating the 2′-OH, whereas the adenine protonates the 5′-oxyanion leaving group. In the other (lower), the roles of the two nucleobases are reversed. At the present time we have no way to distinguish these possibilities; the pH dependence predicted on the basis of the two models would be identical. (B) The VS and hairpin ribozymes may be closely similar in catalytic mechanism. The active geometry of both is generated by loop–loop interaction, and the topological organization of scissile phosphate and the putative catalytic nucleobases is identical in both ribozymes. The hairpin ribozyme utilizes the upper catalytic mechanism shown in (A).