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The bacterial 50S ribosomal subunit 23S rRNA peptidyl transferase center (PTC) is the catalytic core of the ribosome, functioning as a ribozyme to facilitate peptide bond formation during protein synthesis (Polikanov et al., 2014). It is located within a highly conserved pocket of the 23S ribosomal RNA (rRNA) where it coordinates the orientation of the aminoacyl-tRNA in the A-site and the peptidyl-tRNA in the P-site (Wilson, 2014). This site is a major target for diverse antibiotic classes, including oxazolidinones, phenicols, lincosamides, and pleuromutilins, which inhibit bacterial growth by disrupting the translation process (StatPearls, 2023). While these drugs are effective against many Gram-positive and some Gram-negative pathogens, their use is sometimes limited by off-target effects on human mitochondrial ribosomes, which share structural similarities with bacterial ribosomes (Belenkiy et al., 2007). Clinical challenges include the development of resistance through 23S rRNA mutations or enzymatic modifications, such as those mediated by the Cfr methyltransferase (Long et al., 2006). Monitoring for these genetic markers is essential for managing antibiotic efficacy and patient outcomes in clinical settings (PubMed, 2022).
Inhibition of bacterial protein synthesis by binding to the 23S rRNA at the peptidyl transferase center, thereby blocking peptide bond formation or preventing the binding of aminoacyl-tRNA to the A-site.
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