ArticleThe Journal of biological chemistry2016
Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Identification and characterization of a testis-specific glycogen phosphorylase in Kumamoto oyster Crassostrea sikamea.Genetica · 2026Article
- Pentose Phosphate Pathway Is Critical for Providing Energy by Bypassing 6-Phosphofructo-1-Kinase (PFK1) During Increased Neuronal Activity.Metabolites · 2026Review
- The plastidial PHS1-DPE1 complex drives efficient malto-oligosaccharides synthesis in rice starch metabolism.Nature communications · 2026Article
- Structural basis for phosphorylation and allosteric regulation of bacterial glycogen phosphorylase by histidine phosphocarrier protein.Nature communications · 2026Article
- Structural and mechanistic diversity of glycogen phosphorylases from gut bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Biochemical characterization and preliminary X-ray crystallographic analysis of cyanobacterial α-glucan phosphorylases.Acta crystallographica. Section F, Structural biology communications · 2025Article
- Old player, new roles: defining the role of the plastidial phosphorylase.The New phytologist · 2025Review
- Brain Glycogen-Its Metabolic Role in Neuronal Health and Neurological Disorders-An Extensive Narrative Review.Metabolites · 2025Review
- Neural Processing without OPhysiology (Bethesda, Md.) · 2024Review
- Kinetic and Structural Studies of the PlastidialACS omega · 2024Article
- Unveiling the role of PYGB in pancreatic cancer: a novel diagnostic biomarker and gene therapy target.Journal of cancer research and clinical oncology · 2024Article
- Skin single-cell transcriptomics reveals a core of sebaceous gland-relevant genes shared by mice and humans.BMC genomics · 2024Article
- Mechanisms of Cadmium Neurotoxicity.International journal of molecular sciences · 2023Review
- Computational Insights into Novel InhibitorMolecules (Basel, Switzerland) · 2023Article
- Brain Homogenate of a Rat Model of Alzheimer's Disease Modifies the Secretome of 3D Cultured Periodontal Ligament Stem Cells: A Potential Neuroregenerative Therapy.Iranian journal of pharmaceutical research : IJPR · 2022Article
- A Novel 5-Chloro-Molecules (Basel, Switzerland) · 2022Article
- Analysis of the expression, function and signaling of glycogen phosphorylase isoforms in hepatocellular carcinoma.Oncology letters · 2022Article
- A Proteomic Platform Unveils the Brain Glycogen Phosphorylase as a Potential Therapeutic Target for Glioblastoma Multiforme.International journal of molecular sciences · 2022Article
- Discovery and Biotechnological Exploitation of Glycoside-Phosphorylases.International journal of molecular sciences · 2022Review
- Structural Basis for Allostery in PLP-dependent Enzymes.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen.
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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.