ArticleNature2015
Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 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
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Who cites it
102 citing papers in PubMed, 157 citations in OpenAlex.
- A covalent PFKL activator suppresses tumor growth.Nature chemical biology · 2026Article
- The pentose phosphate pathway contributes to excess lactate production in radiation-induced fibroblast to myofibroblast transdifferentiation.The Journal of biological chemistry · 2026Article
- High-Speed AFM Reveals Ligand-Dependent Supramolecular Switching of Human Phosphofructokinase-1.Research square · 2026Article
- ATM promotes PFKP nuclear translocation to balance glycolysis and homologous recombination repair.Nucleic acids research · 2026Article
- Inorganic phosphate and the rapid mobilization of metabolic energy in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The yeast phosphofructokinase β-subunit has RNA unwinding activity and modulates cell cycle progression.Nucleic acids research · 2026Article
- Bidirectional allosteric ligand regulation in a central glycolytic enzyme.bioRxiv : the preprint server for biology · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- F26BP enables control of glycolysis rate independent of energy state.bioRxiv : the preprint server for biology · 2026Article
- PFKP in malignant tumors: bridging metabolic reprogramming, post-translational modifications, and the immunosuppressive microenvironment.Frontiers in cell and developmental biology · 2026Review
- Functional requirements of the liver isoform of phosphofructokinase-1 in breast cancer cell migration.Journal of cell science · 2025Article
- Multiscale Simulation of Phosphofructokinase-1 Assemblies: Capturing the Interplay between Specific and Transient Interactions.The journal of physical chemistry. B · 2025Article
- Activity-dependent citrate dynamics in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Covalent PFKL Activator Suppresses Tumor Growth.bioRxiv : the preprint server for biology · 2025Article
- PFKM phosphorylates histone H3 and promotes mitotic progression by sensing the levels of citrate.Nature communications · 2025Article
- Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- The more we learn, the more diverse it gets: structures, functions and evolution in the Phosphofructokinase Superfamily.The Biochemical journal · 2025Review
- Metabolic reprogramming tailors T cell immunity in sepsis.Frontiers in immunology · 2025Review
- Phosphofructokinase-1 in Cancer: A Promising Target for Diagnosis and Therapy.Recent patents on anti-cancer drug discovery · 2025Review
- Small-molecule inhibitors of 6-phosphofructo-1-kinase simultaneously suppress lactate and superoxide generation in cancer cells.PloS one · 2025Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphofructokinase-1 (PFK1), the 'gatekeeper' of glycolysis, catalyses the committed step of the glycolytic pathway by converting fructose-6-phosphate to fructose-1,6-bisphosphate. Allosteric activation and inhibition of PFK1 by over ten metabolites and in response to hormonal signalling fine-tune glycolytic flux to meet energy requirements. Mutations inhibiting PFK1 activity cause glycogen storage disease type VII, also known as Tarui disease, and mice deficient in muscle PFK1 have decreased fat stores. Additionally, PFK1 is proposed to have important roles in metabolic reprogramming in cancer. Despite its critical role in glucose flux, the biologically relevant crystal structure of the mammalian PFK1 tetramer has not been determined. Here we report the first structures of the mammalian PFK1 tetramer, for the human platelet isoform (PFKP), in complex with ATP-Mg(2+) and ADP at 3.1 and 3.4 Å, respectively. The structures reveal substantial conformational changes in the enzyme upon nucleotide hydrolysis as well as a unique tetramer interface. Mutations of residues in this interface can affect tetramer formation, enzyme catalysis and regulation, indicating the functional importance of the tetramer. With altered glycolytic flux being a hallmark of cancers, these new structures allow a molecular understanding of the functional consequences of somatic PFK1 mutations identified in human cancers. We characterize three of these mutations and show they have distinct effects on allosteric regulation of PFKP activity and lactate production. The PFKP structural blueprint for somatic mutations as well as the catalytic site can guide therapeutic targeting of PFK1 activity to control dysregulated glycolysis in disease.
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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.