A possible mechanism of peptide bond formation on ribosome without mediation of peptidyl transferase

Abstract

Ribosome, the ubiquitous organelle, is the site for protein synthesis in all types of cells. The consecutive peptide bonds are formed by the transpeptidation reaction between carboxyl group of peptidyl moiety and the amino group of the aminoacyl moiety. Both the moieties are attached to the appropiate tRNAs positioned on the ribosome at P and A sites, respectively, through codon-anticodon recognition directed by messenger RNA. The reaction seems to proceed by the nucleophillic attack of the amino group of the aminoacyl tRNA at the A site and on the carboxyl of the ester group of the tRNA at P-site of ribosome. The configuration of the carbon atom of the tetrahedral intermediate may be R or S depending on the direction of the nucleophillic attack. After selecting the favorable conformation of this tetrahedral intermediate quantum mechanical calculations have been carried out to determine the energy needed for its formation. A cyclic intermediate where 2'-OH of the ribose sugar of the P-site tRNA is a member of the ring can be formed from the tetrahedral intermediate. This cyclic intermediate produces a free tRNA and a tRNA attached to a planar peptide unit. Analysis of the energetics using semiempirical method for the formation of a cyclic intermediate indicates that the peptide bond formation through the tetrahedral intermediate in S configuration may not need assistance from any outside agent like an enzyme.