文摘
The action of the peptidyl transferase center of the large ribosomal unit presents a fundamentalstep in the evolution from the RNA world to the protein world. Thus, it is important to understand theorigin of the catalytic power of this ancient enzyme. Earlier studies suggested that the ribosome catalyzespeptide bond formation by using one of its groups as a general base, while more recent works haveproposed that the catalysis is due to proximity effects or to substrate-assisted catalysis. However, theactual nature of the catalytic mechanism remains controversial. This work addresses the origin of thecatalytic power of the ribosome by using computer simulation approaches and comparing the energeticsof the peptide bond formation in the ribosome and in water. It is found that a significant part of theobserved activation entropy of the reference solution reaction is due to solvation entropy, and that theproximity effect is smaller than previously thought. It is also found that the 2'-OH of the A76 ribose,which is associated with a large rate acceleration in the ribosome reaction, does not catalyze peptide bondformation in water. Thus, the catalytic effect cannot be attributed to substrate-assisted catalysis but ratherto the effect of the ribosome on the reacting system. Overall, our calculations indicate that the reductionof the activation free energy is mainly due to electrostatic effects. The nature of these effects and theirrelationship to catalytic factors in modern enzymes is analyzed and discussed.