5tuf

Crystal structure of tetracycline destructase Tet(50) in complex with anhydrotetracycline

spinqualitylabelsall models 5tuf, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tuf is a 2 chain structure with sequence from Uncultivated bacterium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD, SO4, TDC Related: 5tue, 5tui, 5tuk, 5tul, 5tum Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Although tetracyclines are an important class of antibiotics for use in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored, despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes that have a high potential for broad dissemination. Here, we show that tetracycline destructases accommodate tetracycline-class antibiotics in diverse and novel orientations for catalysis, and antibiotic binding drives unprecedented structural dynamics facilitating tetracycline inactivation. We identify a key inhibitor binding mode that locks the flavin adenine dinucleotide cofactor in an inactive state, functionally rescuing tetracycline activity. Our results reveal the potential of a new tetracycline and tetracycline destructase inhibitor combination therapy strategy to overcome resistance by enzymatic inactivation and restore the use of an important class of antibiotics. Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes.,Park J, Gasparrini AJ, Reck MR, Symister CT, Elliott JL, Vogel JP, Wencewicz TA, Dantas G, Tolia NH Nat Chem Biol. 2017 May 8. doi: 10.1038/nchembio.2376. PMID:28481346 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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