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Cited by 423

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Lassomycin, a Ribosomally Synthesized Cyclic Peptide, Kills Mycobacterium tuberculosis by Targeting the ATP-Dependent Protease ClpC1P1P2

Open access
Gavrish, Ekaterina, Sit, Clarissa S., Cao, Shugeng, Kandror, Olga, Spoering, Amy, Peoples, Aaron, Ling, Losee, Fetterman, Ashley, Hughes, Dallas, Bissell, Anthony, Torrey, Heather, Akopian, Tatos, Mueller, Andreas, Epstein, Slava, Goldberg, Alfred, Clardy, Jon, Lewis, Kim·2014·Chemistry & Biology

Abstract

Summary Languishing antibiotic discovery and flourishing antibiotic resistance have prompted development of alternative untapped sources for antibiotic discovery, including previously uncultured bacteria. Here, we screen extracts from uncultured species against M. 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 lassomycin's bacteriocidal activity.

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Metadata

Authors
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.
Venue
Chemistry & Biology
Publisher
Elsevier BV
Published
2014-04
Volume
21
Issue
4
Pages
509-518
ISSN
1074-5521 (ISSN-L)
OpenAlex
W2064744296
Cited by
423
References
5
FWCI
20.35
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Lassomycin, a Ribosomally Synthesized Cyclic Peptide, Kills Mycobacterium tuberculosis by Targeting the ATP-Dependent Protease ClpC1P1P2. https://app.cochat.ai/papers/10.1016/j.chembiol.2014.01.014
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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. (2014). Lassomycin, a Ribosomally Synthesized Cyclic Peptide, Kills Mycobacterium tuberculosis by Targeting the ATP-Dependent Protease ClpC1P1P2. Chemistry & Biology. https://doi.org/10.1016/j.chembiol.2014.01.014

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.