The Structural and Mechanistic Origins of Catalysis in Nucleolytic Ribozymes

Abstract

The nucleolytic ribozymes are a structurally diverse and widespread group of catalytic RNA species. They accelerate transesterification reactions around a million fold, resulting in the site-specific cleavage or ligation of RNA. The potential entities that can participate are the nucleobases, 2′-hydroxyl groups and hydrated metal ions. Probable catalytic strategies are the facilitation of in-line attack, stabilization of the phosphorane transition state, deprotonation of the nucleophile and protonation of the oxyanion leaving group (these last two being general base-acid catalysis).While much of the above was studied in ribozymes such as hammerhead, hairpin and VS, these principles are well illustrated by newer ribozymes. We have solved the crystal structure of the twister ribozyme, which adopts a double pseudoknot fold with a central active site. This well illustrates the four strategies summarized above. We have recently solved the structure of a new ribozyme, that appears mechanistically very different, with a key role for a bound metal ion where an inner-sphere water molecule acts as a general base.