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The bacterial 23S ribosomal RNA (rRNA) is the primary catalytic and structural component of the 50S large ribosomal subunit in prokaryotes (Wilson, 2014, Nature Reviews Microbiology). It forms the peptidyl transferase center (PTC), which is responsible for catalyzing the formation of peptide bonds during protein synthesis (Polikanov et al., 2014, Molecular Cell). Extending from the PTC is the nascent peptide exit tunnel (NPET), a channel composed largely of 23S rRNA through which the growing polypeptide chain must pass to exit the ribosome (Arenz & Wilson, 2016, Cold Spring Harbor Perspectives in Biology). This tunnel is a major pharmacological target for several classes of antibiotics, including macrolides, lincosamides, and oxazolidinones (Dunkle et al., 2010, PNAS). These drugs bind to specific sites on the 23S rRNA, often near the constriction point of the tunnel, to physically obstruct the passage of the nascent peptide or inhibit the catalytic activity of the PTC (Vester & Douthwaite, 2001, Antimicrobial Agents and Chemotherapy). Because the 23S rRNA is highly conserved across bacterial species, it serves as a broad-spectrum target, though mutations or modifications like methylation can lead to significant clinical resistance (Munita & Arias, 2016, Microbiology Spectrum). Understanding the structural interactions within the NPET is crucial for developing next-generation antibiotics that can overcome these resistance mechanisms.
Inhibition of bacterial protein synthesis by binding to the 23S rRNA within the nascent peptide exit tunnel (NPET) or the peptidyl transferase center (PTC), which physically blocks the elongation of the nascent polypeptide chain or prevents peptide bond formation (Wilson, 2014; Polikanov et al., 2014).
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