Distal proton shuttle mechanism of ribosome catalysed peptide bond formation-A theoretical study

Abstract

In this work, we have investigated a novel distal proton shuttle mechanism of ribosome catalyzed peptide bond formation reaction. The reaction was found to follow a two-step mechanism. A distal water molecule located about 6.1 Å away from the attacking amine plays as a proton acceptor and results in a charge-separated intermediate that is stabilized by the N terminus of L27 and the A-site A76 5′-phosphate. The ribose A2451 bridges the proton shuttle pathway, thus plays critical role in the reaction. The calculated 27.64 kcal·mol-1 free energy barrier of the distal proton shuttle mechanism is lower than that of eight-membered ring transition state. The distal proton shuttle mechanism studied in this work can provide new insights into the important biological peptide synthesis process.