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Gentamicin

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Gentamicin is a bactericidal antibiotic that works by irreversibly binding the 30S subunit of the bacterial ribosome, negatively impacting protein synthesis. The primary mechanism of action is generally accepted to work through ablating the ability of the ribosome to discriminate on proper transfer RNA and messenger RNA interactions. Typically, if an incorrect tRNA pairs with an mRNA codon at the aminoacyl site of the ribosome, adenosines 1492 and 1493 are excluded from the interaction and retract, signaling the ribosome to reject the aminoacylated tRNA::Elongation Factor Thermo-Unstable complex. However, when gentamicin binds at helix 44 of the 16S rRNA, it forces the adenosines to maintain the position they take when there is a correct, or cognate, match between aa-tRNA and mRNA. This leads to the acceptance of incorrect aa-tRNAs, causing the ribosome to synthesize proteins with wrong amino acids placed throughout (roughly every 1 in 500). The non-functional, mistranslated proteins misfold and aggregate, eventually leading to death of the bacterium. A secondary mechanism has been proposed based on crystal structures of gentamicin in a secondary binding site at helix 69 of the 23S rRNA, which interacts with helix 44 and proteins that recognize stop codons. At this secondary site, gentamicin is believed to preclude interactions of the ribosome with ribosome recycling factors, causing the two subunits of the ribosome to stay complexed even after translation completes. This creates a pool of inactive ribosomes that can no longer re-intiate and translate new proteins.

Gentamicin can harm your kidneys, and may also cause nerve damage or hearing loss, especially if you have kidney disease or use certain other medicines.


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