Quantum chemical study of ester aminolysis catalyzed by a single adenine: A reference reaction for the ribosomal peptide synthesis

Herein we report the results of a HF/6-31+G** and B3LYP/6-31+G** computatio nal investigation of the title reaction for the peptide bond synthesis cata lyzed by a single adenine. This system constitutes a reference reaction to study the basic chemical events that have been proposed to occur at the pep tidyl transferase active site of ribosomes on the basis of structural deter minations (Science 2000, 239, 920-931). Thus, the analysis of the geometry, charge distribution, and energetics of the critical structures involved in this title reaction yields insight into the catalytic mode of action of RN A molecules. Our computational results give further support to the hypothes es that the activated nucleotide A2451 in the ribosome acts as a base catal yst and that this role is similar to that of the His residue in the catalyt ic triad of serine proteases.