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The Mycobacterium tuberculosis 50S ribosomal subunit 23S rRNA is a fundamental component of the bacterial translation machinery, serving as the catalytic heart of the ribosome (NIH, 2012). It contains the peptidyl transferase center (PTC), which is responsible for forming peptide bonds between amino acids during protein synthesis (NIH, 2022). This molecule is a major therapeutic target for several classes of antibiotics, most notably the oxazolidinones like linezolid and macrolides like clarithromycin, which are essential for treating multidrug-resistant tuberculosis (MDR-TB) (Unisciencepub, 2023). These drugs typically bind to the 23S rRNA to obstruct the assembly of the functional 70S ribosome or to interfere with the elongation of the nascent peptide chain (NIH, 2022). Resistance to these therapies often emerges through specific point mutations in the rrl gene or through the action of methyltransferases like TlyA that modify the rRNA structure (NIH, 2022). A significant clinical challenge associated with targeting this molecule is the potential for off-target effects on human mitochondrial ribosomes, which share structural similarities with bacterial ribosomes, leading to toxicities such as myelosuppression and neuropathy (Healthandme, 2025).
Inhibition of bacterial protein synthesis by binding to the 23S rRNA within the 50S ribosomal subunit, primarily at the peptidyl transferase center (PTC), which prevents the formation of the 70S initiation complex or blocks peptide bond formation and elongation (Unisciencepub, 2023; NIH, 2022).
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