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

Ribosome, the ubiquitous organelle, is the site for protein synthesis in al l types of cells. The consecutive peptide bonds are formed by the transpept idation reaction between carboxyl group of peptidyl moiety and the amino gr oup of the aminoacyl moiety. Both the moieties are attached to the appropia te 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 i ntermediate may be R or S depending on the direction of the nucleophillic a ttack. After selecting the favorable conformation of this tetrahedral inter mediate quantum mechanical calculations have been carried out to determine the energy needed for its formation. A cyclic intermediate where 2'-OH of t he ribose sugar of the P-site tRNA is a member of the ring can be formed fr om the tetrahedral intermediate. This cyclic intermediate produces a free t RNA and a tRNA attached to a planar peptide unit. Analysis of the energetic s using semiempirical method for the formation of a cyclic intermediate ind icates that the peptide bond formation through the tetrahedral intermediate in S configuration may not need assistance from any outside agent like an enzyme (C) 1999 Academic Press.