60S ribosomal subunit peptidyl transferase center (60S PTC)

The peptidyl transferase center (PTC) of the eukaryotic 60S large ribosomal subunit is the highly conserved ribozyme core responsible for catalyzing peptide bond formation during translation (Polacek & Mankin, 2005). It is primarily composed of segments of the 28S ribosomal RNA (rRNA) that coordinate the positioning of aminoacyl-tRNA and peptidyl-tRNA to facilitate the transfer of the growing polypeptide chain (Nissen et al., 2000). While the PTC is a classic target for antibiotics in bacteria, its eukaryotic counterpart is targeted by specific chemotherapeutic agents like omacetaxine mepesuccinate, which binds the A-site to treat chronic myeloid leukemia (Gandhi et al., 2014). Additionally, the PTC is the site of action for various ribosome-inactivating proteins (RIPs) and natural toxins that halt protein synthesis, leading to cell death (Stirpe & Battelli, 2006). Because of its fundamental role in cell viability, the 60S PTC is a focal point for developing inhibitors against rapidly proliferating cancer cells and certain eukaryotic pathogens. However, the high conservation of the PTC across species poses significant challenges for achieving therapeutic selectivity and minimizing systemic toxicity (Schneider-Poetsch et al., 2010).

Other names

Peptidyl transferase centerPTCLarge ribosomal subunit catalytic center28S rRNA catalytic siteRibosomal peptidyltransferase

Inhibition of protein synthesis by sterically blocking the aminoacyl-tRNA binding at the A-site or by interfering with the catalytic transition state of peptide bond formation within the 28S rRNA (Gandhi et al., 2014; Gurel et al., 2009).