A mechanistic study supports a two-step mechanism for peptide bond formation on the ribosome

Abstract

We report the feasible pathways of the quaternary model system for the ribosome-catalyzed PT reaction obtained by density functional calculations. Our results indicate that the step from the reactant complex to the first six-membered TS involving a proton shuttle via the 2'-OH of the P-site A76 in the stepwise pathway is the most favored rate-limiting step in solution. It is found that the C-O3' bond-breaking of A76 is not significant but the C-N bond formation with a tetrahedral intermediate occurs in the rate-limiting step and that the fast breakdown of the C-O3' bond is followed in the second transition state. These are consistent with recent kinetic experiments.