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The peptidyl transferase center (PTC) A-site of the bacterial 23S ribosomal RNA is a critical functional domain within the 50S subunit of the 70S ribosome [1: Wilson, D. N. (2014) Nature Reviews Microbiology]. It serves as the primary docking site for incoming aminoacyl-tRNA molecules, facilitating the alignment necessary for peptide bond formation during protein synthesis [2: Nissen, P., et al. (2000) Science]. As a ribozyme, the 23S rRNA at this site catalyzes the transfer of the growing polypeptide chain from the P-site tRNA to the A-site amino acid [3: Polikanov, Y. S., et al. (2012) Nature Structural & Molecular Biology]. This region is a major therapeutic target for several classes of antibiotics, including oxazolidinones (e.g., linezolid) and amphenicols (e.g., chloramphenicol), which bind to the A-site to physically obstruct tRNA binding or inhibit the catalytic step [4: Leach, K. L., et al. (2007) Molecular Cell]. Clinical challenges associated with this target include the development of resistance through rRNA mutations or methylation, as well as potential toxicity due to structural similarities between bacterial and human mitochondrial ribosomes [5: Long, K. S., & Vester, B. (2012) Antimicrobial Agents and Chemotherapy].
Inhibition of bacterial protein synthesis by sterically blocking the binding of aminoacyl-tRNA to the A-site or interfering with the peptidyl transferase reaction.
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