2M4Q

NMR structure of E. coli ribosomela decoding site with apramycin

2M4Q の概要

• エントリーDOI: 10.2210/pdb2m4q/pdb
• NMR情報: BMRB: 19018
• 分子名称: RNA (27-MER), APRAMYCIN (2 entities in total)
• 機能のキーワード: rna, antibiotic, decoding site, aminoglycoside, apramycin, rna-antibiotic complex, rna/antibiotic
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9195.76

構造登録者

Puglisi, J.D.,Tsai, A.,Marshall, R.,Viani, E. (登録日: 2013-02-10, 公開日: 2013-03-20, 最終更新日: 2024-05-01)

主引用文献

Tsai, A.,Uemura, S.,Johansson, M.,Puglisi, E.V.,Marshall, R.A.,Aitken, C.E.,Korlach, J.,Ehrenberg, M.,Puglisi, J.D.
The impact of aminoglycosides on the dynamics of translation elongation.
Cell Rep, 3:497-508, 2013

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

PubMed: 23416053
DOI: 10.1016/j.celrep.2013.01.027

実験手法

SOLUTION NMR