2XDO

Structure of the Tetracycline degrading Monooxygenase TetX2 from Bacteroides thetaiotaomicron

Summary for 2XDO

• Entry DOI: 10.2210/pdb2xdo/pdb
• Related: 2XYO 2Y6Q 2Y6R
• Descriptor: TETX2 PROTEIN, FLAVIN-ADENINE DINUCLEOTIDE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: tetracycline degradation, tigecycline, flavin, bacteroides fragili, oxidoreductase
• Biological source: BACTEROIDES THETAIOTAOMICRON
• Total number of polymer chains: 4
• Total formula weight: 183204.60

Authors

Volkers, G.,Palm, G.J.,Wright, G.D.,Hinrichs, W. (deposition date: 2010-05-05, release date: 2011-03-23, Last modification date: 2024-05-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.09 Å)