Eukaryotic 60S ribosomal subunit peptidyl transferase center (PTC)

The Eukaryotic 60S ribosomal subunit peptidyl transferase center (PTC) is the highly conserved ribozyme core of the large ribosomal subunit (60S) responsible for catalyzing peptide bond formation during protein synthesis (Polikanov et al., 2014, Molecular Cell). It is primarily composed of segments of the 28S ribosomal RNA (rRNA) that precisely orient the 3' ends of A-site and P-site tRNAs to facilitate the nucleophilic attack of the aminoacyl-tRNA on the peptidyl-tRNA (Nissen et al., 2000, Science). In eukaryotic cells, the PTC is a critical site for translational regulation and a target for various small-molecule inhibitors, including the FDA-approved drug omacetaxine mepesuccinate, which is used to treat chronic myeloid leukemia by blocking the initial step of protein elongation (Gandhi et al., 2014, Clinical Cancer Research). Beyond oncology, the eukaryotic PTC is a target for certain antifungal and antiprotozoal agents that exploit structural differences between host and pathogen ribosomes (Garreau de Loubresse et al., 2014, Nature). However, therapeutic application is often limited by the risk of myelosuppression and potential off-target effects on mitochondrial ribosomes, which can lead to systemic toxicity (Böttger et al., 2001, EMBO Reports). Research continues to explore the PTC as a target for ribosomopathies and viral infections where host translation machinery is hijacked.

Other names

60S PTCPeptidyl transferase centerRibosomal peptidyl transferaseLarge ribosomal subunit catalytic site

Inhibition of peptide bond formation by sterically hindering the binding of aminoacyl-tRNA to the A-site or by interfering with the positioning of the peptidyl-tRNA in the P-site.