Mechanism of Ribosomal Peptide Bond Formation

The mechanism of peptide bond synthesis constitutes a fundamental and long-debated question in molecular biology. For many years, ribosomologists championed a protein-based mechanism, similar to the charge relay system that has been proposed for peptide hydrolysis by serine proteinases [references in (1)]. As it has become apparent that the peptidyl transferase center is composed mainly of RNA, however, two likely mechanisms for catalysis have emerged that are compatible with the available biochemical data: divalent metal ion catalysis (1), or acid-base catalysis mediated by a cytosine (N3) or adenosine (N1, N3). The environment of the catalytic nucleotide would create the unusal higher pK a (whereK a is the acid dissociation constant) necessary for it to behave analogously to the histidine of the serine proteinases. This pK a shift has been shown for a catalytic cytosine in the active site of the hepatitis delta virus ribosome (2).