ArticlePloS one2010
Evolution of allosteric citrate binding sites on 6-phosphofructo-1-kinase.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Pentose Phosphate Pathway Is Critical for Providing Energy by Bypassing 6-Phosphofructo-1-Kinase (PFK1) During Increased Neuronal Activity.Metabolites · 2026Review
- Metabolic pathways fueling human spermatozoa capacitation and hyperactivation: a roadmap for spermatozoa bioenergetics.Frontiers in endocrinology · 2026Review
- Targeting phosphofructokinase in cancer: integrating natural products for metabolic reprogramming and therapeutic innovation.Frontiers in pharmacology · 2026Review
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- Activity-dependent citrate dynamics in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- PFKM phosphorylates histone H3 and promotes mitotic progression by sensing the levels of citrate.Nature communications · 2025Article
- A genetic driver of epileptic encephalopathy impairs gating of synaptic glycolysis.bioRxiv : the preprint server for biology · 2025Article
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- Glutamine Oxidation in Mouse Dorsal Root Ganglia Regulates Pain Resolution and Chronification.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Consequences of the deletion of the major specialized metabolite biosynthetic pathways of Streptomyces coelicolor on the metabolome and lipidome of this strain.Microbial biotechnology · 2024Article
- Citrate serves as a signal molecule to modulate carbon metabolism and iron homeostasis in Staphylococcus aureus.PLoS pathogens · 2024Article
- Site-specific crosslinking reveals Phosphofructokinase-L inhibition drives self-assembly and attenuation of protein interactions.Advances in biological regulation · 2023Article
- Site-Specific Crosslinking Reveals Phosphofructokinase-L Inhibition Drives Self-Assembly and Attenuation of Protein Interactions.bioRxiv : the preprint server for biology · 2023Article
- Review
- Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer.International journal of molecular sciences · 2022Article
- Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells.International journal of molecular sciences · 2022Review
- Treatment against glucose-dependent cancers through metabolic PFKFB3 targeting of glycolytic flux.Cancer metastasis reviews · 2022Review
- A Potential Citrate Shunt in Erythrocytes of PKAN Patients Caused by Mutations in Pantothenate Kinase 2.Biomolecules · 2022Article
- Exogenous d-β-hydroxybutyrate lowers blood glucose in part by decreasing the availability of L-alanine for gluconeogenesis.Endocrinology, diabetes & metabolism · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As an important part of metabolism, metabolic flux through the glycolytic pathway is tightly regulated. The most complex control is exerted on 6-phosphofructo-1-kinase (PFK1) level; this control overrules the regulatory role of other allosteric enzymes. Among other effectors, citrate has been reported to play a vital role in the suppression of this enzyme's activity. In eukaryotes, amino acid residues forming the allosteric binding site for citrate are found both on the N- and the C-terminal region of the enzyme. These site has evolved from the phosphoenolpyruvate/ADP binding site of bacterial PFK1 due to the processes of duplication and tandem fusion of prokaryotic ancestor gene followed by the divergence of the catalytic and effector binding sites. Stricter inhibition of the PFK1 enzyme was needed during the evolution of multi-cellular organisms, and the most stringent control of PFK1 by citrate occurs in vertebrates. By substituting a single amino acid (K557R or K617A) as a component of the allosteric binding site in the C-terminal region of human muscle type PFK-M with a residue found in the corresponding site of a fungal enzyme, the inhibitory effect of citrate was attenuated. Moreover, the proteins carrying these single mutations enabled growth of E. coli transformants encoding mutated human PFK-M in a glucose-containing medium that did not support the growth of E. coli transformed with native human PFK-M. Substitution of another residue at the citrate-binding site (D591V) of human PFK-M resulted in the complete loss of activity. Detailed analyses revealed that the mutated PFK-M subunits formed dimers but were unable to associate into the active tetrameric holoenzyme. These results suggest that stricter control over glycolytic flux developed in metazoans, whose somatic cells are largely characterized by slow proliferation.
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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.