2xdo

Structure of the Tetracycline degrading Monooxygenase TetX2 from Bacteroides thetaiotaomicron

spinqualitylabelsall models 2xdo, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xdo is a 4 chain structure with sequence from "bacillus_thetaiotaomicron"_distaso_1912 "bacillus thetaiotaomicron" distaso 1912. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD, SO4 Related: 2xyo, 2y6q, 2y6r Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The flavin-dependent monooxygenase TetX confers resistance to all clinically relevant tetracyclines, including the recently approved, broad-spectrum antibiotic tigecycline (Tygacil(R)) 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 2.1A 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. Structural basis for a new tetracycline resistance mechanism relying on the TetX monooxygenase.,Volkers G, Palm GJ, Weiss MS, Wright GD, Hinrichs W FEBS Lett. 2011 Mar 16. PMID:21402075 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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