5TUL
Crystal structure of tetracycline destructase Tet(55)
Summary for 5TUL
| Entry DOI | 10.2210/pdb5tul/pdb |
| Related | 5TUE 5TUF 5TUI 5TUK 5TUM |
| Descriptor | Tetracycline destructase Tet(55), PHOSPHATE ION (3 entities in total) |
| Functional Keywords | fad-binding, tetracycline-inactivating, oxidoreductase activity, oxidoreductase |
| Biological source | uncultured bacterium |
| Total number of polymer chains | 1 |
| Total formula weight | 45429.15 |
| Authors | Park, J.,Tolia, N.H. (deposition date: 2016-11-06, release date: 2017-05-10, Last modification date: 2024-03-06) |
| Primary citation | Park, J.,Gasparrini, A.J.,Reck, M.R.,Symister, C.T.,Elliott, J.L.,Vogel, J.P.,Wencewicz, T.A.,Dantas, G.,Tolia, N.H. Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes. Nat. Chem. Biol., 13:730-736, 2017 Cited by PubMed Abstract: 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. PubMed: 28481346DOI: 10.1038/nchembio.2376 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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