Peptidyl transferase activity of tRNA: A quantum chemical study

Abstract

The mechanism of protein synthesis is still unknown due to inability to detect the so-called enzyme "peptidyl transferase" even after elucidation of high-resolution crystal structure of ribosome. We have recently shown by model building and semi-empirical energy calculations that the tRNA molecule at P-site of ribosome may act as peptidyl transferase (Das <i>et al. </i>(1999) <i>J. Theo. Biol. </i>200, 193-205). We proposed that the tetrahedral intermediate formed from nucleophylic attack of CO of P-site amino-acylated tRNA by NH₂ of A-site amino-acy lated tRNA is converted to a six member ring intermediate by conformational change. This ring intermediate produces a free tRNA and a tRNA covalently linked to a peptide. However, energy of the six-member ring intermediate was calculated to be quite high. We show here that the energy values of all the reactants, intermediates and products are within the expected range when they are calculated using high level <i>ab initio </i>quantum chemical methods.