ReviewFrontiers in molecular biosciences2021
Reprogramming of the Caseinolytic Protease by ADEP Antibiotics: Molecular Mechanism, Cellular Consequences, Therapeutic Potential.
Review in Frontiers in molecular biosciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Structural and mechanistic insights into caseinolytic protease inhibition for antimicrobial development against Pseudomonas plecoglossicida.PLoS pathogens · 2026Article
- Article
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- Discovery of coniferaldehyde as an inhibitor of caseinolytic protease to combat Staphylococcus aureus infections.Molecular medicine (Cambridge, Mass.) · 2025Article
- Degradation of Nonribosomal Peptide Synthetase Megasynthetases SrfAA and SrfAB by Acyldepsipeptide-Activated ClpP in Bacillus Subtilis.Chembiochem : a European journal of chemical biology · 2025Article
- Dynamic Oligomerization Processes ofACS omega · 2025Article
- Structure-guided development of selective caseinolytic protease P agonists as antistaphylococcal agents.Cell reports. Medicine · 2024Article
- Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies.Communications biology · 2024Article
- Protein degradation by a component of the chaperonin-linked protease ClpP.Genes to cells : devoted to molecular & cellular mechanisms · 2024Review
- Sophisticated natural products as antibiotics.Nature · 2024Review
- Review
- Molecular insights into the dynamic modulation of bacterial ClpP function and oligomerization by peptidomimetic boronate compounds.Scientific reports · 2024Article
- Bacterial Persister Cells and Development of Antibiotic Resistance in Chronic Infections: An Update.British journal of biomedical science · 2024Review
- Targeting bacterial degradation machinery as an antibacterial strategy.The Biochemical journal · 2023Review
- Systematic analysis of drug combinations against Gram-positive bacteria.Nature microbiology · 2023Article
- Antibiotic Acyldepsipeptides Stimulate themBio · 2022Article
- Acyldepsipeptide Analogues: A Future Generation Antibiotics for Tuberculosis Treatment.Pharmaceutics · 2022Review
- Targeting the Achilles' Heel of Multidrug-ResistantInternational journal of molecular sciences · 2022Article
- Structural insights into ClpP protease side exit pore-opening by a pH drop coupled with substrate hydrolysis.The EMBO journal · 2022Article
- Recent structural insights into the mechanism of ClpP protease regulation by AAA+ chaperones and small molecules.The Journal of biological chemistry · 2022Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rising antibiotic resistance urgently calls for the discovery and evaluation of novel antibiotic classes and unique antibiotic targets. The caseinolytic protease Clp emerged as an unprecedented target for antibiotic therapy 15 years ago when it was observed that natural product-derived acyldepsipeptide antibiotics (ADEP) dysregulated its proteolytic core ClpP towards destructive proteolysis in bacterial cells. A substantial database has accumulated since on the interaction of ADEP with ClpP, which is comprehensively compiled in this review. On the molecular level, we describe the conformational control that ADEP exerts over ClpP, the nature of the protein substrates degraded, and the emerging structure-activity-relationship of the ADEP compound class. On the physiological level, we review the multi-faceted antibacterial mechanism, species-dependent killing modes, the activity against carcinogenic cells, and the therapeutic potential of the compound class.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.