ArticleBiochemistry2006
Identification of the proteasome inhibitor MG262 as a potent ATP-dependent inhibitor of the Salmonella enterica serovar Typhimurium Lon protease.
Article in Biochemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Substrate-Derived Peptides for Selective Covalent Inhibition of Protein Tyrosine Kinases.ACS chemical biology · 2026Article
- Proteostasis-targeted antibacterial strategies.Journal of microbiology (Seoul, Korea) · 2026Review
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- Role of LONP1 in human diseases: molecular mechanisms and therapeutic potential.Cellular & molecular biology letters · 2026Review
- Antibiotic-induced stress responses in Gram-negative bacteria and their role in antibiotic resistance.The Journal of antimicrobial chemotherapy · 2025Review
- Modulation of Lonp1 Activity by Small Compounds.Biomolecules · 2025Review
- A Crucial Role of Proteolysis in the Formation of Intracellular Dinitrosyl Iron Complexes.Molecules (Basel, Switzerland) · 2024Article
- TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A structure and function relationship study to identify the impact of the R721G mutation in the human mitochondrial lon protease.Archives of biochemistry and biophysics · 2021Article
- Identification of key regulators responsible for dysregulated networks in osteoarthritis by large-scale expression analysis.Journal of orthopaedic surgery and research · 2021Article
- Highly Contingent Phenotypes of Lon Protease Deficiency in Escherichia coli upon Antibiotic Challenge.Journal of bacteriology · 2020Article
- Leveraging Peptide Substrate Libraries to Design Inhibitors of Bacterial Lon Protease.ACS chemical biology · 2019Article
- Rbfox-Splicing Factors Maintain Skeletal Muscle Mass by Regulating Calpain3 and Proteostasis.Cell reports · 2018Article
- Utilization of Mechanistic Enzymology to Evaluate the Significance of ADP Binding to Human Lon Protease.Frontiers in molecular biosciences · 2017Article
- Bacterial proteolytic complexes as therapeutic targets.Nature reviews. Drug discovery · 2012Review
- Diphenylarsinic acid promotes degradation of glutaminase C by mitochondrial Lon protease.The Journal of biological chemistry · 2012Article
- Article
- Proteasome inhibitors: an expanding army attacking a unique target.Chemistry & biology · 2012Review
- Mitochondrial calpain 10 is degraded by Lon protease after oxidant injury.Archives of biochemistry and biophysics · 2012Article
- Active-site-directed chemical tools for profiling mitochondrial Lon protease.ACS chemical biology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Lon is a homo-oligomeric ATP-dependent serine protease which functions in the degradation of damaged and certain regulatory proteins. The importance of Lon activity in bacterial pathogenicity has led to its emergence as a target in the development of novel antibiotics. As no potent inhibitors of Lon activity have been reported to date, we sought to identify an inhibitor which could serve as a lead compound in the development of a potent Lon-specific inhibitor. To determine whether a nucleotide- or peptide-based inhibitor would be more effective, we evaluated the steady-state kinetic parameters associated with both ATP and peptide hydrolysis by human and Salmonella enterica serovar Typhimurium Lon. Although the ATP hydrolysis activities of both homologues are kinetically indistinguishable, they display marked differences in peptide substrate specificity. This suggests that a peptide-based inhibitor could be developed which would target bacterial Lon, thereby decreasing side-effects due to cross-reactivity with human Lon. Using Salmonella enterica serovar Typhimurium Lon as a model, we evaluated the IC50 values of a series of commercially available peptide-based inhibitors. Those inhibitors which behave as transition state analogues were the most useful in inhibiting Lon activity. The peptidyl boronate, MG262, was the most potent inhibitor tested (IC50 = 122 +/- 9 nM) and required binding, but not hydrolysis, of ATP to initiate inhibition. We hope to use MG262 as a lead compound in the development of future Lon-specific inhibitors.
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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.