Confluence of theory and experiment reveals the catalytic mechanism of the Varkud satellite ribozyme.

ABSTRACT: The Varkud satellite ribozyme catalyses site-specific RNA cleavage and ligation, and serves as an important model system to understand RNA catalysis. Here, we combine stereospecific phosphorothioate substitution, precision nucleobase mutation and linear free-energy relationship measurements with molecular dynamics, molecular solvation theory and ab initio quantum mechanical/molecular mechanical free-energy simulations to gain insight into the catalysis. Through this confluence of theory and experiment, we unify the existing body of structural and functional data to unveil the catalytic mechanism in unprecedented detail, including the degree of proton transfer in the transition state. Further, we provide evidence for a critical Mg²⁺ in the active site that interacts with the scis

SUBMITTER: Ganguly A 

PROVIDER: S-EPMC7389185 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature