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Pre-50S ribosomal assembly intermediate refers to any of the transient ribonucleoprotein complexes formed during the biogenesis of the large (50S) ribosomal subunit in bacteria. This intricate process involves the coordinated folding of 23S and 5S ribosomal RNAs and the sequential binding of approximately 33 ribosomal proteins, often assisted by assembly factors like RbfA and ObgE (Davis & Williamson, 2017, Nature). These intermediates have gained prominence as therapeutic targets because many clinically relevant antibiotics, such as macrolides and ketolides, disrupt the assembly process in addition to inhibiting the mature ribosome (Champney, 2006, Microbiology). When these drugs bind to precursors, they cause the accumulation of non-functional particles and a subsequent depletion of mature 50S subunits, effectively halting bacterial growth. Research into these intermediates using cryo-electron microscopy has revealed specific structural bottlenecks that can be exploited for the design of novel antimicrobial agents (Jomaa et al., 2011, RNA). Understanding the maturation pathway of the 50S subunit is essential for addressing antibiotic resistance and developing more selective inhibitors.
Inhibition of ribosome biogenesis and assembly
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