ArticleeLife2019
Functional cross-talk between allosteric effects of activating and inhibiting ligands underlies PKM2 regulation.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Energetic Decoding of VSMC Plasticity: Metabolic Reprogramming and Phenotypic Switching.Cardiovascular drugs and therapy · 2026Review
- PKM2: A gatekeeper in macrophage metabolic reprogramming.Journal of pharmaceutical analysis · 2026Review
- Alanine Rewires the Communication Pathways Established During the Allosteric Activation of Liver Pyruvate Kinase by Fructose Bisphosphate.Journal of chemical information and modeling · 2026Article
- PKM2-Mediated Glycolytic Reprogramming in Thyroid Cancer: Mechanistic Insights and Therapeutic Potential.Molecules (Basel, Switzerland) · 2026Review
- GSH as an A-A Type Allosteric Activator of PKM2: Modulating Cancer Cell Homeostasis and Ferroptosis Susceptibility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Isoform-specific regulation of PKM by acetylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Recent progress in the development of small molecule pyruvate kinase M2 inhibitors: 2020-2025.Future medicinal chemistry · 2025Review
- Alpha-ketoglutarate mitigates insulin resistance and metabolic inflexibility in a mouse model of Ataxia-Telangiectasia.Nature communications · 2025Article
- A Novel, Long-Acting, Small Molecule PKM2 Activator and Its Potential Broad Application Against Photoreceptor Degeneration.Translational vision science & technology · 2025Article
- Article
- The roles of molecular chaperones in regulating cell metabolism.FEBS letters · 2023Review
- PKM2 promotes pulmonary fibrosis by stabilizing TGF-β1 receptor I and enhancing TGF-β1 signaling.Science advances · 2022Article
- Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis.Molecular cell · 2022Article
- Targeting allosteric regulation of cancer metabolism.Nature chemical biology · 2022Review
- A Metabolic Reprogramming Amino Acid Polymer as an Immunosurveillance Activator and Leukemia Targeting Drug Carrier for T-Cell Acute Lymphoblastic Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Salvianolic acid A regulates pyroptosis of endothelial cellsFrontiers in pharmacology · 2022Article
- Lactylation of PKM2 Suppresses Inflammatory Metabolic Adaptation in Pro-inflammatory Macrophages.International journal of biological sciences · 2022Article
- Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2.Molecular oncology · 2021Article
- Molecular Simulation Study on the Interaction between Tyrosinase and Flavonoids fromACS omega · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Several enzymes can simultaneously interact with multiple intracellular metabolites, however, how the allosteric effects of distinct ligands are integrated to coordinately control enzymatic activity remains poorly understood. We addressed this question using, as a model system, the glycolytic enzyme pyruvate kinase M2 (PKM2). We show that the PKM2 activator fructose 1,6-bisphosphate (FBP) alone promotes tetramerisation and increases PKM2 activity, but addition of the inhibitor L-phenylalanine (Phe) prevents maximal activation of FBP-bound PKM2 tetramers. We developed a method, AlloHubMat, that uses eigenvalue decomposition of mutual information derived from molecular dynamics trajectories to identify residues that mediate FBP-induced allostery. Experimental mutagenesis of these residues identified PKM2 variants in which activation by FBP remains intact but cannot be attenuated by Phe. Our findings reveal residues involved in FBP-induced allostery that enable the integration of allosteric input from Phe and provide a paradigm for the coordinate regulation of enzymatic activity by simultaneous allosteric inputs.
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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.