Catalytic mechanism of RNA backbone cleavage by ribonuclease H from quantum mechanics/molecular mechanics simulations.

ABSTRACT: We use quantum mechanics/molecular mechanics simulations to study the cleavage of the ribonucleic acid (RNA) backbone catalyzed by ribonuclease H. This protein is a prototypical member of a large family of enzymes that use two-metal catalysis to process nucleic acids. By combining Hamiltonian replica exchange with a finite-temperature string method, we calculate the free energy surface underlying the RNA-cleavage reaction and characterize its mechanism. We find that the reaction proceeds in two steps. In a first step, catalyzed primarily by magnesium ion A and its ligands, a water molecule attacks the scissile phosphate. Consistent with thiol-substitution experiments, a water proton is transferred to the downstream phosphate group. The transient phosphorane formed as a result of this nucle

SUBMITTER: Rosta E 

PROVIDER: S-EPMC3110985 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature