4WOI

4,5-linked aminoglycoside antibiotics regulate the bacterial ribosome by targeting dynamic conformational processes within intersubunit bridge B2

これはPDB形式変換不可エントリーです。

4WOI の概要

• エントリーDOI: 10.2210/pdb4woi/pdb
• 関連するPDBエントリー: 4GAQ 4GAR 4GAS 4GAU
• 分子名称: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (60 entities in total)
• 機能のキーワード: protein biosynthesis, ribosomes, paromomycin, antibiotic translocation, rna, trna, transfer, exit, peptidyl, 30s, 70s, 16s, ribosomal subunit, ribosome
• 由来する生物種: Escherichia coli str. K-12 substr. MDS42; 詳細
• タンパク質・核酸の鎖数: 110
• 化学式量合計: 4419077.67

構造登録者

Pulk, A.,Cate, J.H.D.,Blanchard, S.,Wasserman, M.,Altman, R.,Zhou, Z.,Zinder, J.,Green, K.,Garneau-Tsodikova, S. (登録日: 2014-10-15, 公開日: 2015-08-05, 最終更新日: 2024-11-13)

主引用文献

Wasserman, M.R.,Pulk, A.,Zhou, Z.,Altman, R.B.,Zinder, J.C.,Green, K.D.,Garneau-Tsodikova, S.,Doudna Cate, J.H.,Blanchard, S.C.
Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions.
Nat Commun, 6:7896-7896, 2015

PubMed Abstract: Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin-paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6'-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6'-substituent and the drug's net positive charge. By solving the crystal structure of the paromomycin-ribosome complex, we observe specific contacts between the apical tip of H69 and the 6'-hydroxyl on paromomycin from within the drug's canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation.

PubMed: 26224058
DOI: 10.1038/ncomms8896

実験手法

X-RAY DIFFRACTION (3 Å)