2MAI
NMR structure of lassomycin
Summary for 2MAI
| Entry DOI | 10.2210/pdb2mai/pdb |
| NMR Information | BMRB: 19355 |
| Descriptor | Lassomycin (1 entity in total) |
| Functional Keywords | lasso, antibiotic |
| Biological source | Lentzea kentuckyensis |
| Total number of polymer chains | 1 |
| Total formula weight | 1901.27 |
| Authors | Gavrish, E.,Sit, C.S.,Kandror, O.,Spoering, A.,Peoples, A.,Ling, L.,Fetterman, A.,Hughes, D.,Cao, S.,Bissell, A.,Torrey, H.,Akopian, T.,Mueller, A.,Epstein, S.,Goldberg, A.,Clardy, J.,Lewis, K. (deposition date: 2013-07-09, release date: 2014-05-07, Last modification date: 2023-11-15) |
| Primary citation | Gavrish, E.,Sit, C.S.,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. Lassomycin, a Ribosomally Synthesized Cyclic Peptide, Kills Mycobacterium tuberculosis by Targeting the ATP-Dependent Protease ClpC1P1P2. Chem.Biol., 21:509-518, 2014 Cited by PubMed Abstract: 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. PubMed: 24684906DOI: 10.1016/j.chembiol.2014.01.014 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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