80S ribosome peptidyl transferase center (80S PTC) (80S PTC)

The 80S ribosome peptidyl transferase center (80S PTC) is the catalytic heart of the eukaryotic ribosome, located within the 60S large ribosomal subunit (Khatter et al., 2015, Nature). It is a ribozyme where ribosomal RNA (rRNA) catalyzes the formation of peptide bonds between amino acids during the elongation phase of protein synthesis (Polikanov et al., 2014, Molecular Cell). The PTC provides the structural framework to correctly orient the aminoacyl-tRNA in the A-site and the peptidyl-tRNA in the P-site for the nucleophilic attack required for chain elongation (Polikanov et al., 2018, Front. Mol. Biosci.). In clinical medicine, the 80S PTC is a validated therapeutic target; for instance, omacetaxine mepesuccinate (homoharringtonine) is an FDA-approved drug for chronic myeloid leukemia that binds to the A-site cleft of the PTC to block protein synthesis (Gandhi et al., 2014, Therapeutic Advances in Hematology). While many antibiotics selectively target the bacterial 70S ribosome, the 80S PTC is also targeted by various natural toxins and experimental anti-cancer agents, though achieving selectivity over healthy eukaryotic cells remains a significant challenge (Garreau de Loubresse et al., 2014, Nature). Inhibition of the PTC often leads to the depletion of short-lived oncogenic proteins like MYC and MCL1, making it a potent point of intervention in oncology (Cancers, 2021, 13(17)).

Other names

Eukaryotic peptidyl transferase center60S ribosomal subunit peptidyl transferase centerRibosomal PTCPeptidyltransferase

The 80S ribosome peptidyl transferase center is inhibited by drugs that bind to the A-site or P-site, sterically blocking the accommodation of aminoacyl-tRNAs or preventing the nucleophilic attack required for peptide bond formation, thereby halting translation elongation (Gandhi et al., 2014, Therapeutic Advances in Hematology; Polikanov et al., 2018, Front. Mol. Biosci.).