ArticleThe Journal of biological chemistry2020
Biochemical and structural insights into how amino acids regulate pyruvate kinase muscle isoform 2.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- PKM2-Mediated Glycolytic Reprogramming in Thyroid Cancer: Mechanistic Insights and Therapeutic Potential.Molecules (Basel, Switzerland) · 2026Review
- A neutrophil-intrinsic CKLF1-PKM2 axis drives glycolytic flux for de novo DAG synthesis and pro-inflammatory ROS production.Cell death and differentiation · 2026Article
- VeGA-RX and VeGA-SCX: Controllable SMARTS-Guided Generative Transformers for Precision-DrivenJournal of chemical information and modeling · 2026Article
- The mechanism of PKM2/HIF-1α axis polarizing TAMs by upregulating glucose-serine metabolism to promote melanoma progression.Frontiers in immunology · 2026Article
- VeGA: A Versatile Generative Architecture for Bioactive Molecules across Multiple Therapeutic Targets.Journal of chemical information and modeling · 2025Article
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Abrogating the adenine methylation ability of Lacticaseibacillus paracasei improves its freeze-drying and storage resistance.NPJ science of food · 2025Article
- Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- The role of PKM2 in cancer progression and its structural and biological basis.Journal of physiology and biochemistry · 2024Review
- Article
- PYK-SubstitutionOME: an integrated database containing allosteric coupling, ligand affinity and mutational, structural, pathological, bioinformatic and computational information about pyruvate kinase isozymes.Database : the journal of biological databases and curation · 2023Article
- Identification of residues involved in allosteric signal transmission from amino acid binding site of pyruvate kinase muscle isoform 2.PloS one · 2023Article
- Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway.Nature communications · 2022Article
- miR-1307 promotes hepatocarcinogenesis by CALR-OSTC-endoplasmic reticulum protein folding pathway.iScience · 2021Article
- Tumor pyruvate kinase M2 modulators: a comprehensive account of activators and inhibitors as anticancer agents.RSC medicinal chemistry · 2021Review
- Article
- Structural basis for allosteric regulation of pyruvate kinase M2 by phosphorylation and acetylation.The Journal of biological chemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.
Indexed as
Identifiers
What OpenQuestion holds
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.