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The bacterial 23S ribosomal RNA of the 50S ribosomal subunit is a large, ~2900 nucleotide RNA molecule that constitutes the functional and structural core of the bacterial large ribosomal subunit (50S). It forms complex secondary and tertiary structures divided into six domains, with domain V containing the peptidyl transferase center, crucial for catalyzing peptide bond formation during protein synthesis. The 23S rRNA provides the scaffold for ribosomal proteins, facilitates tRNA interactions, and is essential for bacterial growth and survival. Due to its pivotal roles and unique sequence features, 23S rRNA is the molecular target for several major classes of antibiotics, which inhibit bacterial translation by binding to specific regions of the RNA—most commonly domain V—thus blocking protein synthesis and suppressing bacterial proliferation. Mutations or methylation in the 23S rRNA can confer resistance to these drugs, representing a significant challenge in infectious disease therapy.
Inhibition of peptidyl transferase activity (blocks peptide bond formation); Prevention of tRNA translocation and/or binding at catalytic site; Allosteric modification of ribosomal structure, leading to improper protein synthesis and/or ribosome stalling; Targeting domain V, the key functional region bound by many antibiotics.
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