23S ribosomal RNA peptidyl-tRNA site (P-site) of the 50S bacterial ribosomal subunit (23S rRNA P-site)

The 23S ribosomal RNA (rRNA) P-site (peptidyl-tRNA site) is a highly conserved functional domain within the 50S large subunit of the bacterial ribosome (NCBI, 2023). It serves as the critical binding site for the tRNA molecule carrying the growing polypeptide chain during the elongation phase of translation (PubMed, 2021). Located at the heart of the peptidyl transferase center (PTC), the P-site is essential for catalyzing peptide bond formation by orienting the peptidyl-tRNA to react with the incoming aminoacyl-tRNA in the A-site (Nature, 2017). This site is a major pharmacological target for several classes of antibiotics, most notably the oxazolidinones (e.g., Linezolid) and pleuromutilins (e.g., Lefamulin), which bind to the PTC and physically obstruct the binding or movement of tRNA (StatPearls, 2023). Disruption of P-site function effectively halts bacterial protein synthesis, leading to bacteriostatic or bactericidal effects depending on the pathogen. Clinical resistance often involves point mutations in the 23S rRNA, such as the G2576T substitution, or the acquisition of methyltransferase enzymes like Cfr that modify the rRNA to prevent drug binding (PubMed, 2020).

Other names

Peptidyl-tRNA siteP-site of the 50S subunit23S rRNA peptidyl transferase center P-siteRibosomal P-site

Inhibition of bacterial protein synthesis by binding to the peptidyl transferase center (PTC) and preventing the proper positioning or translocation of peptidyl-tRNA, thereby halting peptide bond formation.