Nucleolytic RNA enzymes (ribozymes) catalyze a transesterification reaction where the nucleophilic 2'-O attacks the scissile phosphate and displaces the 5'-O. The nucleophilic 2'OH must be deprotonated at some point along the reaction pathway for this process to occur. Many ribozymes contain a nearby guanine suspected to function as general base. However, 2'-OH moieties and guanines exhibit considerably different unperturbed pKa values such that proton transfer would be highly unfavorable. We postulate that nearby hydrogen bond donors, such as the exocyclic amine of guanine, serve to lower the pKa of the nucleophilic 2'-OH, priming the alcohol for deprotonation and subsequent nucleophilic attack. We will present our findings from molecular dynamic simulations which offer insight into this potential driving force.

Evaluating hydrogen bonding to the nucleophilic 2'OH in ribozymes as a driving force for catalysis

2019 Fall National Meeting

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