Bacterial 50S ribosomal subunit peptidyl transferase center (P-site) (50S PTC)

The bacterial 50S ribosomal subunit is the large component of the 70S ribosome, responsible for catalyzing peptide bond formation during protein synthesis. A critical functional region within this subunit is the peptidyl transferase center (PTC), which includes the P-loop of the 23S rRNA. This site interacts specifically with the 3' CCA-end of the peptidyl-tRNA, positioning it for the nucleophilic attack required to extend the polypeptide chain. Many potent antibiotics, such as pleuromutilins (e.g., lefamulin) and oxazolidinones, target this secondary site or adjacent pockets to disrupt translation. By binding to the P-site or the P-loop, these drugs physically obstruct the proper alignment of tRNA substrates, effectively halting bacterial growth. Because this site is highly conserved in bacteria but differs significantly from the eukaryotic cytosolic ribosome, it serves as an effective target for selective toxicity, although similarities with human mitochondrial ribosomes can lead to clinical side effects.

Other names

23S rRNA P-loopPeptidyl transferase centerP-site tRNA binding pocketRibosomal 50S subunit P-siteLarge ribosomal subunit P-site

Inhibition of protein synthesis by binding to the peptidyl transferase center (PTC) and preventing the correct positioning of the 3' CCA-end of tRNA in the P-site, thereby blocking peptide bond formation.