2MAI

NMR structure of lassomycin

2MAI の概要

• エントリーDOI: 10.2210/pdb2mai/pdb
• NMR情報: BMRB: 19355
• 分子名称: Lassomycin (1 entity in total)
• 機能のキーワード: lasso, antibiotic
• 由来する生物種: Lentzea kentuckyensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1901.27

構造登録者

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. (登録日: 2013-07-09, 公開日: 2014-05-07, 最終更新日: 2023-11-15)

主引用文献

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

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: 24684906
DOI: 10.1016/j.chembiol.2014.01.014

実験手法

SOLUTION NMR