Mechanism of peptide bond formation on the ribosome

Abstract

1. The ribosome 2042. Peptide bond formation is catalyzed by RNA 2053. Characteristics of the uncatalyzed reaction 2074. Potential catalytic strategies of the ribosome 2075. Experimental systems 2086. Substrate binding in the PT center 2107. Induced fit in the active site 2118. pH dependence of peptide bond formation 2129. Reaction with full-length aa-tRNA 21410. Role of active-site residues 21511. pH-dependent structural changes of the active site 21612. Entropic catalysis 21713. Role of 2′-OH of A76 in P-site tRNA 21814. Catalysis by proton shuttling 21915. Plasticity of the active site 22016. Conclusions 22117. Acknowledgments 22218. References 222Peptide bond formation is the fundamental reaction of ribosomal protein synthesis. The ribosome's active site – the peptidyl transferase center – is composed of rRNA, and thus the ribosome is the largest known RNA catalyst. The ribosome accelerates peptide bond formation by 107-fold relative to the uncatalyzed reaction. Recent progress of structural, biochemical and computational approaches has provided a fairly detailed picture of the catalytic mechanisms employed by the ribosome. Energetically, catalysis is entirely entropic, indicating an important role of solvent reorganization, substrate positioning, and/or orientation of the reacting groups within the active site. The ribosome provides a pre-organized network of electrostatic interactions that stabilize the transition state and facilitate proton shuttling involving ribose hydroxyl groups of tRNA. The catalytic mechanism employed by the ribosome suggests how ancient RNA-world enzymes may have functioned.