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Mycobacterium tuberculosis 23S ribosomal RNA (23S rRNA) is a fundamental structural and catalytic component of the 50S large ribosomal subunit in the causative agent of tuberculosis (NCBI: Gene ID 885011). It functions as a ribozyme, providing the peptidyl transferase activity necessary for peptide bond formation during protein translation. As an essential element of the bacterial translation machinery, it serves as a primary therapeutic target for several important classes of antibiotics, including oxazolidinones like linezolid and macrolides like clarithromycin (PMID: 25135898). These drugs typically bind to highly conserved regions such as the peptidyl transferase center or the exit tunnel, effectively halting bacterial growth. However, clinical resistance often arises through specific point mutations in the rrl gene encoding the 23S rRNA. Additionally, because human mitochondrial ribosomes share structural similarities with bacterial ribosomes, drugs targeting the 23S rRNA can cause off-target effects, leading to toxicities such as myelosuppression and neuropathy during long-term therapy (PMID: 12821452).
Inhibition of bacterial protein synthesis by binding to the 50S ribosomal subunit, specifically at the peptidyl transferase center (PTC) or the nascent peptide exit tunnel (NPET), thereby blocking peptide bond formation or peptide translocation (PMID: 12462144).
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