ArticleThe Journal of biological chemistry2018
The oligomerization state of bacterial enzyme I (EI) determines EI's allosteric stimulation or competitive inhibition by α-ketoglutarate.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 17 citations in OpenAlex.
- Integrating NMR and contact-response analysis reveals the allosteric network driving domain closure in Enzyme I.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Beyond structures: solution NMR as the quantitative engine of integrated structural biology.Frontiers in molecular biosciences · 2026Review
- Environmental regulation of toxin production in Bacillus anthracis.PLoS pathogens · 2025Article
- Environmental Regulation of Toxin Production inbioRxiv : the preprint server for biology · 2025Article
- Elucidation of the Mechanisms of Inter-domain Coupling in the Monomeric State of Enzyme I by High-pressure NMR.Journal of molecular biology · 2024Article
- Solution Structure Ensembles of the Open and Closed Forms of the ∼130 kDa Enzyme I via AlphaFold Modeling, Coarse Grained Simulations, and NMR.Journal of the American Chemical Society · 2023Article
- Protein Conformational Dynamics Underlie Selective Recognition of Thermophilic over Mesophilic Enzyme I by a Substrate Analogue.Biomolecules · 2023Article
- State-selective frustration as a key driver of allosteric pluripotency.Chemical science · 2021Article
- Structure elucidation of the elusive Enzyme I monomer reveals the molecular mechanisms linking oligomerization and enzymatic activity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Single Point Mutation Controls the Rate of Interconversion Between theFrontiers in molecular biosciences · 2021Article
- Hybrid Thermophilic/Mesophilic Enzymes Reveal a Role for Conformational Disorder in Regulation of Bacterial Enzyme I.Journal of molecular biology · 2020Article
- Allosteric pluripotency as revealed by protein kinase A.Science advances · 2020Article
- N-terminal fusion of the N-terminal domain of bacterial enzyme I facilitates recombinant expression and purification of the human RNA demethylases FTO and Alkbh5.Protein expression and purification · 2020Article
- An allosteric pocket for inhibition of bacterial Enzyme I identified by NMR-based fragment screening.Journal of structural biology: X · 2020Article
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
The bacterial phosphotransferase system (PTS) is a signal transduction pathway that couples phosphoryl transfer to active sugar transport across the cell membrane. The PTS is initiated by phosphorylation of enzyme I (EI) by phosphoenolpyruvate (PEP). The EI phosphorylation state determines the phosphorylation states of all other PTS components and is thought to play a central role in the regulation of several metabolic pathways and to control the biology of bacterial cells at multiple levels, for example, affecting virulence and biofilm formation. Given the pivotal role of EI in bacterial metabolism, an improved understanding of the mechanisms controlling its activity could inform future strategies for bioengineering and antimicrobial design. Here, we report an enzymatic assay, based on Selective Optimized Flip Angle Short Transient (SOFAST) NMR experiments, to investigate the effect of the small-molecule metabolite α-ketoglutarate (αKG) on the kinetics of the EI-catalyzed phosphoryl transfer reaction. We show that at experimental conditions favoring the monomeric form of EI, αKG promotes dimerization and acts as an allosteric stimulator of the enzyme. However, when the oligomerization state of EI is shifted toward the dimeric species, αKG functions as a competitive inhibitor of EI. We developed a kinetic model that fully accounted for the experimental data and indicated that bacterial cells might use the observed interplay between allosteric stimulation and competitive inhibition of EI by αKG to respond to physiological fluctuations in the intracellular environment. We expect that the mechanism for regulating EI activity revealed here is common to several other oligomeric enzymes.
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