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

The bacterial 50S ribosomal subunit P-site region near the tRNA CCA terminus is a vital component of the peptidyl transferase center (PTC), the catalytic heart of the ribosome (Wilson, 2014, Nature Reviews Microbiology). This specific region facilitates the alignment of the 3' CCA end of the peptidyl-tRNA, which carries the growing polypeptide chain, ensuring it is correctly positioned for the formation of a new peptide bond (Dunkle et al., 2010, Science). Composed primarily of highly conserved 23S ribosomal RNA (rRNA) nucleotides, this site is essential for the elongation phase of bacterial protein synthesis. It serves as a major pharmacological target for several classes of antibiotics, including lincosamides like clindamycin and pleuromutilins like lefamulin, which bind within the PTC to sterically hinder tRNA placement or catalytic activity (Polikanov et al., 2015, Molecular Cell; Paukner & Riedl, 2017, Cold Spring Harbor Perspectives in Medicine). These drugs are primarily used to treat infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). However, the clinical utility of targeting this site is often challenged by the development of resistance mechanisms, such as rRNA methylation by the Cfr enzyme or point mutations in the 23S rRNA, which can reduce drug binding affinity (Long & Vester, 2012, Antibiotics).

Other names

Ribosomal P-site23S rRNA P-sitePeptidyl transferase center P-site50S P-siteRibosomal peptidyl site

Inhibition of peptidyl transferase activity by preventing the proper positioning of the CCA-end of peptidyl-tRNA in the P-site, thereby blocking peptide bond formation (Wilson, 2014, Nature Reviews Microbiology).