ArticleACS infectious diseases2019
High-Resolution Structure of ClpC1-Rufomycin and Ligand Binding Studies Provide a Framework to Design and Optimize Anti-Tuberculosis Leads.
Article in ACS infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Small-molecule activators of theiScience · 2026Article
- Phosphoarginine modulates oligomerization and repressor activity of mycobacterial ClpC2.bioRxiv : the preprint server for biology · 2026Article
- Review
- ClpC1-targeting peptide natural products differentially dysregulate the proteome of Mycobacterium tuberculosis.Nature communications · 2026Article
- Antimycobacterial peptides as natural therapeutics for tuberculosis: mechanisms and structural features.Frontiers in antibiotics · 2026Review
- Allosteric control of the bacterial ClpC/ClpP protease and its hijacking by antibacterial peptides.The EMBO journal · 2025Article
- Mutations in ClpC1 or ClpX subunit of caseinolytic protease confer resistance to ilamycins in mycobacteria.Communications biology · 2025Article
- Total Syntheses of Stereoisomeric Congeners of Rufomycin Natural Products Having Anti-Mycobacterial Activity.Organic letters · 2025Article
- The Identification of Novel Mutations in ATP-Dependent Protease ClpC1 Assists in the Molecular Diagnosis of Obscured Pyrazinamide-Resistant Tuberculosis Clinical Isolates.Microorganisms · 2025Article
- Enhancing rufomycin production by CRISPR/Cas9-based genome editing and promoter engineering inSynthetic and systems biotechnology · 2025Article
- Structure-Based Analysis of Semisynthetic Anti-TB Rufomycin Analogues.Journal of natural products · 2025Article
- The Biarylitides: Understanding the Structure and Biosynthesis of a Fascinating Class of Cytochrome P450 Modified RiPP Natural Products.Chembiochem : a European journal of chemical biology · 2025Review
- Characterization of RufT Thioesterase Domain Reveals Insights into Rufomycin Cyclization and the Biosynthetic Origin of Rufomyazine.ACS chemical biology · 2025Article
- MdfA is a novel ClpC adaptor protein that functions in the developingGenes & development · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development.Scientific reports · 2025Article
- Rapid Peptide Cyclization Inspired by the Modular Logic of Nonribosomal Peptide Synthetases.Journal of the American Chemical Society · 2024Article
- Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria.Nature communications · 2024Article
- The Antitubercular Activities of Natural Products with Fused-Nitrogen-Containing Heterocycles.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeting bacterial degradation machinery as an antibacterial strategy.The Biochemical journal · 2023Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Addressing the urgent need to develop novel drugs against drug-resistant Mycobacterium tuberculosis ( M. tb) strains, ecumicin (ECU) and rufomycin I (RUFI) are being explored as promising new leads targeting cellular proteostasis via the caseinolytic protein ClpC1. Details of the binding topology and chemical mode of (inter)action of these cyclopeptides help drive further development of novel potency-optimized entities as tuberculosis drugs. ClpC1 M. tb protein constructs with mutations driving resistance to ECU and RUFI show reduced binding affinity by surface plasmon resonance (SPR). Despite certain structural similarities, ECU and RUFI resistant mutation sites did not overlap in their SPR binding patterns. SPR competition experiments show ECU prevents RUFI binding, whereas RUFI partially inhibits ECU binding. The X-ray structure of the ClpC1-NTD-RUFI complex reveals distinct differences compared to the previously reported ClpC1-NTD-cyclomarin A structure. Surprisingly, the complex structure revealed that the epoxide moiety of RUFI opened and covalently bound to ClpC1-NTD via the sulfur atom of Met1. Furthermore, RUFI analogues indicate that the epoxy group of RUFI is critical for binding and bactericidal activity. The outcomes demonstrate the significance of ClpC1 as a novel target and the importance of SAR analysis of identified macrocyclic peptides for drug discovery.
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