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The small-subunit ribosomal RNA (ssu rRNA), comprising the 16S rRNA in prokaryotes and the 18S rRNA in eukaryotes, is the primary molecular target for aminoglycoside antibiotics such as neomycin and G418 (Geneticin) (Vicens & Westhof, 2003). These rRNA molecules are central to the translation process, specifically facilitating the accurate decoding of mRNA by the ribosome (Mingeot-Leclercq et al., 1999). Aminoglycosides bind to the aminoacyl-tRNA binding site (A-site) of the ssu rRNA, inducing a conformational change that mimics the state of correct codon-anticodon pairing, which leads to the incorporation of incorrect amino acids and the production of mistranslated proteins (StatPearls, 2023). While neomycin is used clinically to treat bacterial infections by targeting the 16S rRNA, G418 is a broader-spectrum agent that also targets the eukaryotic 18S rRNA, making it a standard selection tool in molecular biology for identifying cells carrying resistance genes (PubChem CID 123865). Beyond their role as antibiotics, these interactions are being explored for nonsense suppression therapy in genetic diseases where aminoglycosides can induce read-through of premature stop codons (Nudelman et al., 2009). However, therapeutic application is frequently constrained by significant safety concerns, most notably nephrotoxicity and ototoxicity, which arise from the drugs' accumulation in the renal cortex and inner ear (StatPearls, 2023).
Aminoglycosides bind to the A-site of the small ribosomal subunit (16S rRNA in bacteria or 18S rRNA in eukaryotes), inducing a conformational change that leads to mRNA misreading and inhibition of translocation (Vicens & Westhof, 2003; Mingeot-Leclercq et al., 1999).
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