The Impact of Aminoglycosides on the Dynamics of Translation Elongation

摘要: Inferring antibiotic mechanisms on translation through static structures has been challenging, as biological systems are highly dynamic. Dynamic single-molecule methods also limited to few simultaneously measurable parameters. We have circumvented these limitations with a multifaceted approach investigate three structurally distinct aminoglycosides that bind the aminoacyl-transfer RNA site (A site) in prokaryotic 30S ribosomal subunit: apramycin, paromomycin, and gentamicin. Using several fluorescence measurements combined structural biochemical techniques, we observed changes translational dynamics for each aminoglycoside. While all drugs effectively inhibit elongation, their actions mechanistically distinct. Apramycin does not displace A1492 A1493 at decoding center, demonstrated by solution nuclear magnetic resonance structure, causing only miscoding; instead, it primarily blocks translocation. Paromomycin gentamicin, which A1493, cause significant miscoding, block intersubunit rotation, Our results show power of dynamics, structural, approaches elucidate complex underlying its inhibition.