Ribosomal A-site of the large ribosomal subunit (50S A-site)

The ribosomal A-site (aminoacyl site) of the large ribosomal subunit (50S in bacteria) is a critical functional region where the incoming aminoacyl-tRNA binds to deliver an amino acid for incorporation into the growing polypeptide chain [Wilson, 2014, Nature Reviews Microbiology]. Located adjacent to the peptidyl transferase center (PTC), this site ensures the correct positioning of the tRNA for peptide bond formation [Polikanov et al., 2014, Molecular Cell]. It is a major target for several classes of antibiotics, including oxazolidinones (e.g., linezolid), lincosamides (e.g., clindamycin), and pleuromutilins (e.g., lefamulin), which disrupt bacterial protein synthesis [StatPearls, 2023]. By binding to the A-site, these drugs can physically block the entry of tRNA or induce conformational changes that halt translation [Dunkle et al., 2010, Science]. Because of the structural similarities between bacterial ribosomes and human mitochondrial ribosomes, drugs targeting this site can sometimes cause off-target toxicity, such as myelosuppression or neuropathy [Bancroft et al., 2010, Antimicrobial Agents and Chemotherapy]. Understanding the molecular architecture of the A-site is essential for developing new antimicrobial agents to combat multi-drug resistant bacterial strains [Poehlsgaard & Douthwaite, 2005, Nature Reviews Microbiology].

Other names

Aminoacyl-tRNA binding site of the 50S subunit50S A-sitePeptidyl transferase center A-site23S rRNA A-site

Inhibition of bacterial protein synthesis by binding to the 23S rRNA within the A-site of the 50S subunit, thereby preventing the proper positioning of aminoacyl-tRNA or inhibiting the peptidyl transferase reaction [Wilson, 2014; StatPearls, 2023].