ArticleEMBO molecular medicine2009
The antibiotic ADEP reprogrammes ClpP, switching it from a regulated to an uncontrolled protease.
Article in EMBO molecular medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed.
- Small-molecule activators of theiScience · 2026Article
- Proteotoxic Stress Bioreporter Enables Mechanism-Informed Antibiotic Discovery.Journal of natural products · 2026Article
- Expression patterns of core metabolic genes and elevated intracellular ROS confer drug tolerance inMicrobiology spectrum · 2026Article
- Proteostasis-targeted antibacterial strategies.Journal of microbiology (Seoul, Korea) · 2026Review
- Structural and mechanistic insights into caseinolytic protease inhibition for antimicrobial development against Pseudomonas plecoglossicida.PLoS pathogens · 2026Article
- Development and evaluation of mitochondria-targeted caseinolytic protease (ClpP) agonist chemical probes in in vitro breast cancer models.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Article
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- Degradation of Nonribosomal Peptide Synthetase Megasynthetases SrfAA and SrfAB by Acyldepsipeptide-Activated ClpP in Bacillus Subtilis.Chembiochem : a European journal of chemical biology · 2025Article
- ClpP2 proteasomes and SpxA1 determine Listeria monocytogenes tartrolon B hyper-resistance.PLoS genetics · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Dynamic Oligomerization Processes ofACS omega · 2025Article
- Unraveling the mechanism of small molecule induced activation of Staphylococcus aureus signal peptidase IB.Communications biology · 2024Article
- Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024Review
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
- Article
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- ClpP/ClpX deficiency impairs mitochondrial functions and mTORC1 signaling during spermatogenesis.Communications biology · 2023Article
- Acyldepsipeptide Antibiotics and a Bioactive Fragment Thereof Differentially PerturbACS chemical biology · 2023Article
- Membrane Proteins as a Regulator for Antibiotic Persistence in Gram-Negative Bacteria.Journal of microbiology (Seoul, Korea) · 2023Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A novel class of antibiotic acyldepsipeptides (designated ADEPs) exerts its unique antibacterial activity by targeting the peptidase caseinolytic protease P (ClpP). ClpP forms proteolytic complexes with heat shock proteins (Hsp100) that select and process substrate proteins for ClpP-mediated degradation. Here, we analyse the molecular mechanism of ADEP action and demonstrate that ADEPs abrogate ClpP interaction with cooperating Hsp100 adenosine triphosphatases (ATPases). Consequently, ADEP treated bacteria are affected in ClpP-dependent general and regulatory proteolysis. At the same time, ADEPs also activate ClpP by converting it from a tightly regulated peptidase, which can only degrade short peptides, into a proteolytic machinery that recognizes and degrades unfolded polypeptides. In vivo nascent polypeptide chains represent the putative primary target of ADEP-activated ClpP, providing a rationale for the antibacterial activity of the ADEPs. Thus, ADEPs cause a complete functional reprogramming of the Clp-protease complex.
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