4GUV

TetX derivatized with Xenon

Summary for 4GUV

• Entry DOI: 10.2210/pdb4guv/pdb
• Related: 2XDO 2XYO 2Y6Q 2Y6R
• Descriptor: TetX2 protein, FLAVIN-ADENINE DINUCLEOTIDE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: rossmann fold, monooxygenase, xenon, oxidoreductase
• Biological source: Bacteroides thetaiotaomicron
• Total number of polymer chains: 4
• Total formula weight: 184062.82

Authors

Volkers, G.,Palm, G.J.,Panjikar, S.,Hinrichs, W. (deposition date: 2012-08-29, release date: 2013-04-10, Last modification date: 2023-09-13)

Primary citation

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, 69:1758-1767, 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

Experimental method

X-RAY DIFFRACTION (2.73 Å)