ArticleCell2022
BacPROTACs mediate targeted protein degradation in bacteria.
Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed.
- Small-molecule activators of theiScience · 2026Article
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Structure-function analysis of the bacterial ClpE-ClpP AAA+ protease.The Journal of biological chemistry · 2026Article
- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- From Epigenetic Regulation to Protein Degradation: Emerging Strategies for Anti-Infective Drug Discovery.International journal of molecular sciences · 2026Review
- Differential contributions of ClpX and ClpP to pulmonary virulence in classical and hypervirulentInfection and immunity · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Proteostasis-targeted antibacterial strategies.Journal of microbiology (Seoul, Korea) · 2026Review
- Prenatal cadmium exposure and male infertility in mice: A multi-generational mechanistic study.Eco-Environment & Health · 2026Article
- From Host-Derived Pressures to the Environmental Anti-Antimicrobial Peptides Resistome: Mechanisms, Reservoirs and Implications for Therapeutic Peptide Design.Marine drugs · 2026Review
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Approaches to Study Proteins Encoded by Essential Genes.Proteins · 2026Review
- ClpC1-targeting peptide natural products differentially dysregulate the proteome of Mycobacterium tuberculosis.Nature communications · 2026Article
- SsrA-Based Targeted Protein Degradation in Escherichia coli.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Antechokinetics, the kinetics of antimicrobial resistance molecules.Frontiers in pharmacology · 2026Review
- Utilizing nanoinducers for precision degradation of bacterial protein to mitigate antibiotic resistance.Nature communications · 2025Article
- Light-Activated Metal-Dependent Protein Degradation: A Heterobifunctional Ruthenium(II) Photosensitizer Targeting New Delhi Metallo-β-lactamase 1.Journal of the American Chemical Society · 2025Article
- Ketoboronate as a Minimal Covalent-Reversible Tag for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins.Journal of the American Chemical Society · 2025Article
- Synthesis of a Conformationally Fixed Bicyclomarin Derivative.ChemMedChem · 2025Article
- Protein degradation-based anti-infective drug research.Acta pharmaceutica Sinica. B · 2025Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hijacking the cellular protein degradation system offers unique opportunities for drug discovery, as exemplified by proteolysis-targeting chimeras. Despite their great promise for medical chemistry, so far, it has not been possible to reprogram the bacterial degradation machinery to interfere with microbial infections. Here, we develop small-molecule degraders, so-called BacPROTACs, that bind to the substrate receptor of the ClpC:ClpP protease, priming neo-substrates for degradation. In addition to their targeting function, BacPROTACs activate ClpC, transforming the resting unfoldase into its functional state. The induced higher-order oligomer was visualized by cryo-EM analysis, providing a structural snapshot of activated ClpC unfolding a protein substrate. Finally, drug susceptibility and degradation assays performed in mycobacteria demonstrate in vivo activity of BacPROTACs, allowing selective targeting of endogenous proteins via fusion to an established degron. In addition to guiding antibiotic discovery, the BacPROTAC technology presents a versatile research tool enabling the inducible degradation of bacterial proteins.
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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.