ArticleJournal of chemical information and modeling2016
Synergistic Allosteric Mechanism of Fructose-1,6-bisphosphate and Serine for Pyruvate Kinase M2 via Dynamics Fluctuation Network Analysis.
Article in Journal of chemical information and modeling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Alanine Rewires the Communication Pathways Established During the Allosteric Activation of Liver Pyruvate Kinase by Fructose Bisphosphate.Journal of chemical information and modeling · 2026Article
- A mechanovascular framework for pre-neoplastic microenvironmental dysregulation and early carcinogenesis.Frontiers in oncology · 2026Article
- High-Resolution Molecular-Dynamics Simulations of the Pyruvate Kinase Muscle Isoform 1 and 2 (PKM1/2).Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases.Molecular neurobiology · 2024Review
- Quantifying the large-scale chromosome structural dynamics during the mitosis-to-G1 phase transition of cell cycle.Open biology · 2023Article
- The Replicative DnaE Polymerase ofLife (Basel, Switzerland) · 2023Article
- An allosteric regulation mechanism of Arabidopsis Serine/Threonine kinase 1 (SIK1) through phosphorylation.Computational and structural biotechnology journal · 2022Article
- Structural basis for allosteric regulation of pyruvate kinase M2 by phosphorylation and acetylation.The Journal of biological chemistry · 2020Article
- Biochemical and structural insights into how amino acids regulate pyruvate kinase muscle isoform 2.The Journal of biological chemistry · 2020Article
- Dynamical important residue network (DIRN): network inference via conformational change.Bioinformatics (Oxford, England) · 2019Article
- Article
- Order-disorder transition of intrinsically disordered kinase inducible transactivation domain of CREB.The Journal of chemical physics · 2018Article
- Synergistic regulation mechanism of iperoxo and LY2119620 for muscarinic acetylcholine M2 receptor.RSC advances · 2018Article
- PKM2 in carcinogenesis and oncotherapy.Oncotarget · 2017Review
- Allosteric pyruvate kinase-based "logic gate" synergistically senses energy and sugar levels in Mycobacterium tuberculosis.Nature communications · 2017Article
- Structure-Activity Relationship in TLR4 Mutations: Atomistic Molecular Dynamics Simulations and Residue Interaction Network Analysis.Scientific reports · 2017Article
- Conformation Dynamics of the Intrinsically Disordered Protein c-Myb with theRSC advances · 2017Article
- Allosteric pathways in tetrahydrofolate sensing riboswitch with dynamics correlation network.Molecular bioSystems · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Pyruvate kinase M2 (PKM2) plays a key role in tumor metabolism and regulates the rate-limiting final step of glycolysis. In tumor cells, there are two allosteric effectors for PKM2: fructose-1,6-bisphosphate (FBP) and serine. However, the relationship between FBP and serine for allosteric regulation of PKM2 is unknown. Here we constructed residue/residue fluctuation correlation network based on all-atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in bound PKM2 is distinctly different from that in the free state, FBP/PKM2, or Ser/PKM2. The community network analysis indicates that the information can freely transfer from the allosteric sites of FBP and serine to the substrate site in bound PKM2, while there exists a bottleneck for information transfer in the network of the free state. Furthermore, the binding free energy between the substrate and PKM2 for bound PKM2 is significantly lower than either of FBP/PKM2 or Ser/PKM2. Thus, a hypothesis of "synergistic allosteric mechanism" is proposed for the allosteric regulation of FBP and serine. This hypothesis was further confirmed by the perturbational and mutational analyses of community networks and binding free energies. Finally, two possible synergistic allosteric pathways of FBP-K433-T459-R461-A109-V71-R73-MG2-OXL and Ser-I47-C49-R73-MG2-OXL were identified based on the shortest path algorithm and were confirmed by the network perturbation analysis. Interestingly, no similar pathways could be found in the free state. The process targeting on the allosteric pathways can better regulate the glycolysis of PKM2 and significantly inhibit the progression of tumor.
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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.