5TUL

Crystal structure of tetracycline destructase Tet(55)

5TUL の概要

• エントリーDOI: 10.2210/pdb5tul/pdb
• 関連するPDBエントリー: 5TUE 5TUF 5TUI 5TUK 5TUM
• 分子名称: Tetracycline destructase Tet(55), PHOSPHATE ION (3 entities in total)
• 機能のキーワード: fad-binding, tetracycline-inactivating, oxidoreductase activity, oxidoreductase
• 由来する生物種: uncultured bacterium
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45429.15

構造登録者

Park, J.,Tolia, N.H. (登録日: 2016-11-06, 公開日: 2017-05-10, 最終更新日: 2024-03-06)

主引用文献

Park, J.,Gasparrini, A.J.,Reck, M.R.,Symister, C.T.,Elliott, J.L.,Vogel, J.P.,Wencewicz, T.A.,Dantas, G.,Tolia, N.H.
Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes.
Nat. Chem. Biol., 13:730-736, 2017

PubMed Abstract: Although tetracyclines are an important class of antibiotics for use in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored, despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes that have a high potential for broad dissemination. Here, we show that tetracycline destructases accommodate tetracycline-class antibiotics in diverse and novel orientations for catalysis, and antibiotic binding drives unprecedented structural dynamics facilitating tetracycline inactivation. We identify a key inhibitor binding mode that locks the flavin adenine dinucleotide cofactor in an inactive state, functionally rescuing tetracycline activity. Our results reveal the potential of a new tetracycline and tetracycline destructase inhibitor combination therapy strategy to overcome resistance by enzymatic inactivation and restore the use of an important class of antibiotics.

PubMed: 28481346
DOI: 10.1038/nchembio.2376

実験手法

X-RAY DIFFRACTION (2 Å)