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The bacterial 70S ribosome peptidyl transferase center (PTC) is the catalytic core of the large (50S) ribosomal subunit, responsible for the fundamental chemical reactions of protein synthesis: peptide bond formation and peptide release [3, 7, 9]. As a ribozyme, its activity is primarily mediated by the highly conserved 23S ribosomal RNA (rRNA) rather than ribosomal proteins [7, 11, 13]. The PTC serves as a critical therapeutic target for a diverse array of antibiotics, particularly those used to treat infections caused by Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) [1, 6, 16]. Drugs targeting this site, including oxazolidinones, lincosamides, and pleuromutilins, typically act by sterically hindering the binding or proper orientation of aminoacyl-tRNA and peptidyl-tRNA, thereby halting translation elongation [1, 5, 14, 17]. While highly effective, these agents face challenges such as the emergence of resistance through rRNA mutations or enzymatic modifications (e.g., Cfr methylation) and potential off-target effects on human mitochondrial ribosomes, which share structural similarities with the bacterial target [1, 6, 15, 16].
Inhibition of peptide bond formation by sterically hindering the binding or positioning of aminoacyl-tRNA and peptidyl-tRNA within the catalytic site.
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