4A99

STRUCTURE OF THE TETRACYCLINE DEGRADING MONOOXYGENASE TETX IN COMPLEX WITH MINOCYCLINE

4A99 の概要

• エントリーDOI: 10.2210/pdb4a99/pdb
• 関連するPDBエントリー: 2XDO 2XYO 2Y6Q 2Y6R
• 分子名称: TETX2 PROTEIN, FLAVIN-ADENINE DINUCLEOTIDE, (4S,4AS,5AR,12AS)-4,7-BIS(DIMETHYLAMINO)-3,10,12,12A-TETRAHYDROXY-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2- CARBOXAMIDE, ... (5 entities in total)
• 機能のキーワード: flavoprotein, tetracycline degradation, monooxygenase, flavin
• 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: 186576.22

構造登録者

Volkers, G.,Palm, G.J.,Weiss, M.S.,Hinrichs, W. (登録日: 2011-11-25, 公開日: 2012-12-12, 最終更新日: 2023-12-20)

主引用文献

Volkers, G.,Damas, J.M.,Palm, G.J.,Panjikar, S.,Soares, C.M.,Hinrichs, W.
Putative Dioxygen-Binding Sites and Recognition of Tigecycline and Minocycline in the Tetracycline-Degrading Monooxygenase Tetx
Acta Crystallogr.,Sect.D, 69:1758-, 2013

PubMed Abstract: Expression of the aromatic hydroxylase TetX under aerobic conditions confers bacterial resistance against tetracycline antibiotics. Hydroxylation inactivates and degrades tetracyclines, preventing inhibition of the prokaryotic ribosome. X-ray crystal structure analyses of TetX in complex with the second-generation and third-generation tetracyclines minocycline and tigecycline at 2.18 and 2.30 Å resolution, respectively, explain why both clinically potent antibiotics are suitable substrates. Both tetracyclines bind in a large tunnel-shaped active site in close contact to the cofactor FAD, pre-oriented for regioselective hydroxylation to 11a-hydroxytetracyclines. The characteristic bulky 9-tert-butylglycylamido substituent of tigecycline is solvent-exposed and does not interfere with TetX binding. In the TetX-minocycline complex a second binding site for a minocycline dimer is observed close to the active-site entrance. The pocket is formed by the crystal packing arrangement on the surface of two neighbouring TetX monomers. Crystal structure analysis at 2.73 Å resolution of xenon-pressurized TetX identified two adjacent Xe-binding sites. These putative dioxygen-binding cavities are located in the substrate-binding domain next to the active site. Molecular-dynamics simulations were performed in order to characterize dioxygen-diffusion pathways to FADH2 at the active site.

PubMed: 23999299
DOI: 10.1107/S0907444913013802

実験手法

X-RAY DIFFRACTION (2.18 Å)