ArticleBiochemistry2014
Understanding the structural requirements for activators of the Kef bacterial potassium efflux system.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Structure and mechanism of the KNature communications · 2024Article
- Macromolecular Crowding, Phase Separation, and Homeostasis in the Orchestration of Bacterial Cellular Functions.Chemical reviews · 2024Review
- The Potassium Efflux System Kef: Bacterial Protection against Toxic Electrophilic Compounds.Membranes · 2023Review
- Isolation and Genomics ofMicrobiology spectrum · 2023Article
- Two Color Imaging of Different Hypoxia Levels in Cancer Cells.Journal of the American Chemical Society · 2023Article
- Synergistic Combination of Facile Thiol-Maleimide Derivatization and Supramolecular Solvent-Based Microextraction for UHPLC-HRMS Analysis of Glutathione in Biofluids.Frontiers in chemistry · 2021Article
- Article
- Acidification of Cytoplasm in Escherichia coli Provides a Strategy to Cope with Stress and Facilitates Development of Antibiotic Resistance.Scientific reports · 2020Article
- Response of the Biocontrol Agent Pseudomonas pseudoalcaligenes AVO110 to Rosellinia necatrix Exudate.Applied and environmental microbiology · 2019Article
- Genome-wide mutation analysis ofGut pathogens · 2019Article
- Adenosine Monophosphate Binding Stabilizes the KTN Domain of the Shewanella denitrificans Kef Potassium Efflux System.Biochemistry · 2017Article
- Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions.Journal of medicinal chemistry · 2017Article
- Bacterial Responses to Glyoxal and Methylglyoxal: Reactive Electrophilic Species.International journal of molecular sciences · 2017Review
- Transcriptomics Indicates Active and Passive Metronidazole Resistance Mechanisms in Three SeminalFrontiers in microbiology · 2017Article
- The photochemical thiol-ene reaction as a versatile method for the synthesis of glutathioneOrganic chemistry frontiers : an international journal of organic chemistry · 2016Article
- Enzymatic properties, evidence for in vivo expression, and intracellular localization of shewasin D, the pepsin homolog from Shewanella denitrificans.Scientific reports · 2016Article
- Comprehensive molecular characterization of Methylobacterium extorquens AM1 adapted for 1-butanol tolerance.Biotechnology for biofuels · 2016Article
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Authors and funding
11 authors.
Funding
Abstract
The potassium efflux system, Kef, protects bacteria against the detrimental effects of electrophilic compounds via acidification of the cytoplasm. Kef is inhibited by glutathione (GSH) but activated by glutathione-S-conjugates (GS-X) formed in the presence of electrophiles. GSH and GS-X bind to overlapping sites on Kef, which are located in a cytosolic regulatory domain. The central paradox of this activation mechanism is that GSH is abundant in cells (at concentrations of ∼10-20 mM), and thus, activating ligands must possess a high differential over GSH in their affinity for Kef. To investigate the structural requirements for binding of a ligand to Kef, a novel fluorescent reporter ligand, S-{[5-(dimethylamino)naphthalen-1-yl]sulfonylaminopropyl} glutathione (DNGSH), was synthesized. By competition assays using DNGSH, complemented by direct binding assays and thermal shift measurements, we show that the well-characterized Kef activator, N-ethylsuccinimido-S-glutathione, has a 10-20-fold higher affinity for Kef than GSH. In contrast, another native ligand that is a poor activator, S-lactoylglutathione, exhibits a similar Kef affinity to GSH. Synthetic ligands were synthesized to contain either rigid or flexible structures and investigated as ligands for Kef. Compounds with rigid structures and high affinity activated Kef. In contrast, flexible ligands with similar binding affinities did not activate Kef. These data provide insight into the structural requirements for Kef gating, paving the way for the development of a screen for potential therapeutic lead compounds targeting the Kef system.
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