50S ribosomal subunit peptidyl transferase center (PTC)

The 50S ribosomal subunit peptidyl transferase center (PTC) is the catalytic core of the bacterial ribosome, responsible for the formation of peptide bonds during protein synthesis (Polikanov et al., 2014, PubMed). Located within the highly conserved 23S ribosomal RNA (rRNA) of the large (50S) subunit, the PTC acts as a ribozyme that precisely orients the aminoacyl-tRNA and peptidyl-tRNA to facilitate the nucleophilic attack required for polypeptide chain elongation (Wilson, 2014, Nature Reviews Microbiology). Because of its essential role in bacterial survival and its structural divergence from the eukaryotic 80S ribosome, the PTC is a primary target for several major classes of antibiotics, including macrolides, oxazolidinones, lincosamides, and pleuromutilins (Dunkle et al., 2010, PNAS). These drugs typically bind within or near the PTC to physically block the addition of new amino acids or obstruct the nascent peptide exit tunnel (Leach et al., 2007, Molecular Microbiology). However, the clinical utility of targeting the PTC is increasingly challenged by resistance mechanisms such as rRNA methylation (e.g., by the Cfr enzyme) or specific point mutations that reduce drug binding affinity (Long et al., 2006, Antimicrobial Agents and Chemotherapy). Furthermore, since human mitochondrial ribosomes share structural similarities with bacterial ribosomes, some PTC-targeting drugs can cause off-target effects like myelosuppression or neuropathy due to the inhibition of mitochondrial protein synthesis (Ames et al., 2005, Clinical Infectious Diseases).

Other names

Peptidyl transferase center23S rRNA peptidyl transferase centerRibosomal peptidyl transferaseLarge ribosomal subunit catalytic center

Inhibition of bacterial protein synthesis by blocking the peptidyl transferase reaction or sterically hindering the nascent peptide exit tunnel.