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The 23S ribosomal RNA (rRNA) is the central catalytic component of the large (50S) subunit of the bacterial ribosome, acting as a ribozyme to facilitate protein synthesis (Polacek & Mankin, 2005). Within this molecule, the peptidyl transferase center (PTC) is the specific site where peptide bond formation occurs between the aminoacyl-tRNA and the peptidyl-tRNA (Nissen et al., 2000). Because of its fundamental role in bacterial survival, the PTC is a major target for several classes of antibiotics, including macrolides, oxazolidinones, lincosamides, and pleuromutilins (Wilson, 2014). These drugs typically bind to the PTC or the adjacent nascent peptide exit tunnel, physically preventing the elongation of the protein chain (Dunkle et al., 2010). Resistance to these agents frequently arises through point mutations in the 23S rRNA or through enzymatic modifications, such as methylation by Erm or Cfr enzymes, which alter the drug-binding pocket (Vester & Douthwaite, 2001). Furthermore, the structural similarity between bacterial 23S rRNA and human mitochondrial rRNA can lead to off-target effects, such as mitochondrial toxicity and myelosuppression, which are key considerations in the clinical use of these antibiotics (Leach et al., 2007).
Inhibition of bacterial protein synthesis by binding to the peptidyl transferase center (PTC) of the 23S rRNA, which either directly blocks peptide bond formation or sterically obstructs the nascent peptide exit tunnel (Wilson, 2014; Dunkle et al., 2010).
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