Peptidyltransferase

Peptidyl transferase refers to the catalytic activity of the ribosome that forms peptide bonds during protein synthesis. It transfers the growing polypeptide from the 3'-end of the peptidyl-tRNA in the P site to the amino group of the aminoacyl-tRNA in the A site, producing a new peptide bond and releasing a deacylated tRNA from the P site. This reaction occurs within the peptidyl transferase center of the large ribosomal subunit.

The catalytic center is composed largely of ribosomal RNA. In bacteria, the functional core is within domain V of the 23S rRNA; in eukaryotes and archaea, analogous regions of the 28S rRNA (60S subunit) provide the activity. Although ribosomal proteins surround the site, the core catalysis is RNA-based, leading to the view of the ribosome as a ribozyme. The exact mechanism remains a topic of study, but it is generally described as the amino group of the A-site tRNA attacking the carbonyl carbon of the peptidyl-tRNA, with substrate positioning and proton transfers facilitated by the rRNA and a network of water molecules; the involvement of the 2' hydroxyl of the P-site tRNA is discussed in various models.

Antibiotics and inhibitors often target the peptidyl transferase center to block protein synthesis in bacteria. Examples include chloramphenicol and hygromycin B. Puromycin, a mimic of aminoacyl-tRNA, can enter the A site and cause premature termination by accepting the growing polypeptide, illustrating the PTC’s substrate-binding properties.