2mai

NMR structure of lassomycin

spinqualitylabelsall models 2mai Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mai is a 1 chain structure with sequence from Lentzea kentuckyensis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: ILM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Languishing antibiotic discovery and flourishing antibiotic resistance have prompted the development of alternative untapped sources for antibiotic discovery, including previously uncultured bacteria. Here, we screen extracts from uncultured species against Mycobacterium tuberculosis and identify lassomycin, an antibiotic that exhibits potent bactericidal activity against both growing and dormant mycobacteria, including drug-resistant forms of M. tuberculosis, but little activity against other bacteria or mammalian cells. Lassomycin is a highly basic, ribosomally encoded cyclic peptide with an unusual structural fold that only partially resembles that of other lasso peptides. We show that lassomycin binds to a highly acidic region of the ClpC1 ATPase complex and markedly stimulates its ATPase activity without stimulating ClpP1P2-catalyzed protein breakdown, which is essential for viability of mycobacteria. This mechanism, uncoupling ATPase from proteolytic activity, accounts for the bactericidal activity of lassomycin. Lassomycin, a Ribosomally Synthesized Cyclic Peptide, Kills Mycobacterium tuberculosis by Targeting the ATP-Dependent Protease ClpC1P1P2.,Gavrish E, Sit CS, Cao S, Kandror O, Spoering A, Peoples A, Ling L, Fetterman A, Hughes D, Bissell A, Torrey H, Akopian T, Mueller A, Epstein S, Goldberg A, Clardy J, Lewis K Chem Biol. 2014 Apr 24;21(4):509-18. doi: 10.1016/j.chembiol.2014.01.014. Epub, 2014 Mar 27. PMID:24684906 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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