5J91

Structure of the Wild-type 70S E coli ribosome bound to Tigecycline

これはPDB形式変換不可エントリーです。

5J91 の概要

• エントリーDOI: 10.2210/pdb5j91/pdb
• 関連するPDBエントリー: 5IT8 5J5B 5J7L 5J88 5J8A 5JC9
• 分子名称: 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (70 entities in total)
• 機能のキーワード: tigecycline, ribosome, escherichia coli, ribosome-inhibitor complex, ribosome-antibiotic complex, ribosome/antibiotic
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 105
• 化学式量合計: 4272877.52

構造登録者

Cocozaki, A.,Ferguson, A. (登録日: 2016-04-08, 公開日: 2016-07-06, 最終更新日: 2025-03-19)

主引用文献

Cocozaki, A.I.,Altman, R.B.,Huang, J.,Buurman, E.T.,Kazmirski, S.L.,Doig, P.,Prince, D.B.,Blanchard, S.C.,Cate, J.H.,Ferguson, A.D.
Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors.
Proc.Natl.Acad.Sci.USA, 113:8188-8193, 2016

PubMed Abstract: Mutations conferring resistance to translation inhibitors often alter the structure of rRNA. Reduced susceptibility to distinct structural antibiotic classes may, therefore, emerge when a common ribosomal binding site is perturbed, which significantly reduces the clinical utility of these agents. The translation inhibitors negamycin and tetracycline interfere with tRNA binding to the aminoacyl-tRNA site on the small 30S ribosomal subunit. However, two negamycin resistance mutations display unexpected differential antibiotic susceptibility profiles. Mutant U1060A in 16S Escherichia coli rRNA is resistant to both antibiotics, whereas mutant U1052G is simultaneously resistant to negamycin and hypersusceptible to tetracycline. Using a combination of microbiological, biochemical, single-molecule fluorescence transfer experiments, and X-ray crystallography, we define the specific structural defects in the U1052G mutant 70S E. coli ribosome that explain its divergent negamycin and tetracycline susceptibility profiles. Unexpectedly, the U1052G mutant ribosome possesses a second tetracycline binding site that correlates with its hypersusceptibility. The creation of a previously unidentified antibiotic binding site raises the prospect of identifying similar phenomena in antibiotic-resistant pathogens in the future.

PubMed: 27382179
DOI: 10.1073/pnas.1605127113

実験手法

X-RAY DIFFRACTION (2.96 Å)