2Y6R

Structure of the TetX monooxygenase in complex with the substrate 7- chlortetracycline

2Y6R の概要

• エントリーDOI: 10.2210/pdb2y6r/pdb
• 関連するPDBエントリー: 2XDO 2XYO 2Y6Q
• 分子名称: TETX2 PROTEIN, FLAVIN-ADENINE DINUCLEOTIDE, 7-CHLOROTETRACYCLINE, ... (5 entities in total)
• 機能のキーワード: oxidoreductase, antibiotic resistance, flavin, tigecycline, tetracycline degradation
• 由来する生物種: BACTEROIDES THETAIOTAOMICRON
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 184463.43

構造登録者

Volkers, G.,Palm, G.J.,Weiss, M.S.,Wright, G.D.,Hinrichs, W. (登録日: 2011-01-25, 公開日: 2011-03-23, 最終更新日: 2023-12-20)

主引用文献

Volkers, G.,Palm, G.J.,Weiss, M.S.,Wright, G.D.,Hinrichs, W.
Structural Basis for a New Tetracycline Resistance Mechanism Relying on the Tetx Monooxygenase.
FEBS Lett., 585:1061-, 2011

PubMed Abstract: The flavin-dependent monooxygenase TetX confers resistance to all clinically relevant tetracyclines, including the recently approved, broad-spectrum antibiotic tigecycline (Tygacil®) which is a critical last-ditch defense against multidrug-resistant pathogens. TetX represents the first resistance mechanism against tigecycline, which circumvents both the tet-gene encoded resistances, relying on active efflux of tetracyclines, and ribosomal protection proteins. The alternative enzyme-based mechanism of TetX depends on regioselective hydroxylation of tetracycline antibiotics to 11a-hydroxy-tetracyclines. Here, we report the X-ray crystallographic structure determinations at 2.1Å resolution of native TetX from Bacteroides thetaiotaomicron and its complexes with tetracyclines. Our crystal structures explain the extremely versatile substrate diversity of the enzyme and provide a first step towards the rational design of novel tetracycline derivatives to counter TetX-based resistance prior to emerging clinical observations.

PubMed: 21402075
DOI: 10.1016/J.FEBSLET.2011.03.012

実験手法

X-RAY DIFFRACTION (3.1 Å)