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The bacterial 70S ribosomal peptidyl transferase center (PTC) is the essential catalytic site located within the 50S subunit of the bacterial ribosome, responsible for the formation of peptide bonds during protein synthesis (Wilson, 2014). It is a ribozyme, meaning its activity is primarily driven by the 23S ribosomal RNA (rRNA) rather than ribosomal proteins (Polikanov et al., 2014). The PTC facilitates the reaction between the peptidyl-tRNA in the P-site and the aminoacyl-tRNA in the A-site, a process critical for both the initiation and elongation phases of translation (Dunkle et al., 2010). Because of its central role in bacterial growth and replication, the PTC is a major target for several classes of antibiotics, including oxazolidinones, macrolides, lincosamides, and pleuromutilins (Wilson, 2014). These drugs bind to specific pockets within the PTC to sterically hinder the binding of tRNA or the progression of the nascent polypeptide chain (Polikanov et al., 2014). While the PTC is highly conserved among bacteria, its structural divergence from the human 80S ribosome allows for selective toxicity, though potential cross-reactivity with human mitochondrial ribosomes remains a clinical concern (Long & Vester, 2003; StatPearls, 2023). Resistance to these antibiotics often arises through mutations in the 23S rRNA or the acquisition of methyltransferase enzymes like Cfr, which modify the PTC to prevent drug binding (Long & Vester, 2003).
Inhibition of bacterial protein synthesis by binding to the 23S rRNA of the 50S ribosomal subunit at the peptidyl transferase center (PTC), which prevents the formation of the peptide bond or blocks the ribosomal exit tunnel (Wilson, 2014; Polikanov et al., 2014).
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