ArticleMolecular biology of the cell2017
Reconstituted IMPDH polymers accommodate both catalytically active and inactive conformations.
Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 83 citations in OpenAlex.
- Inosine monophosphate dehydrogenases are key players for functional development in Arabidopsis.The Plant journal : for cell and molecular biology · 2026Article
- Structural basis for allosteric regulation of mycobacterial guanosine 5´-monophosphate reductase by ATP and GTP.Nature communications · 2026Article
- Imaging Techniques for the Study of Protein Condensates and Filaments and Their Applications.International journal of molecular sciences · 2026Review
- Enzyme Assemblies in Nucleotide Metabolism: Structure, Regulation, and Disease Implications.Advances in experimental medicine and biology · 2026Review
- An IMPDH2 variant associated with neurodevelopmental disorder disrupts purine biosynthesis and somite organization.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Y12C mutation disrupts IMPDH cytoophidia and alters cancer metabolism.The FEBS journal · 2025Article
- IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency.EMBO reports · 2024Article
- Two-metal ion mechanism of DNA cleavage by activated, filamentous SgrAI.The Journal of biological chemistry · 2024Article
- The IMPDH cytoophidium couples metabolism and fetal development in mice.Cellular and molecular life sciences : CMLS · 2024Article
- Light-sensitive phosphorylation regulates retinal IMPDH1 activity and filament assembly.The Journal of cell biology · 2024Article
- A journey into the regulatory secrets of theFrontiers in pharmacology · 2024Review
- Agglomeration: when folded proteins clump together.Biophysical reviews · 2023Review
- Insight into the role of the Bateman domain at the molecular and physiological levels through engineered IMP dehydrogenases.Protein science : a publication of the Protein Society · 2023Article
- Neurodevelopmental disorder mutations in the purine biosynthetic enzyme IMPDH2 disrupt its allosteric regulation.The Journal of biological chemistry · 2023Article
- Article
- Structural basis of human PRPS2 filaments.Cell & bioscience · 2023Article
- Effect on cell survival and cytoophidium assembly of the adRP-10-related IMPDH1 missense mutation Asp226Asn.Frontiers in cell and developmental biology · 2023Article
- Host Cell Amplification of Nutritional Stress Contributes To Persistence in Chlamydia trachomatis.mBio · 2022Article
- The role of filamentation in activation and DNA sequence specificity of the sequence-specific endonuclease SgrAI.Biochemical Society transactions · 2022Article
- The gateway to guanine nucleotides: Allosteric regulation of IMP dehydrogenases.Protein science : a publication of the Protein Society · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Several metabolic enzymes undergo reversible polymerization into macromolecular assemblies. The function of these assemblies is often unclear but in some cases they regulate enzyme activity and metabolic homeostasis. The guanine nucleotide biosynthetic enzyme inosine monophosphate dehydrogenase (IMPDH) forms octamers that polymerize into helical chains. In mammalian cells, IMPDH filaments can associate into micron-length assemblies. Polymerization and enzyme activity are regulated in part by binding of purine nucleotides to an allosteric regulatory domain. ATP promotes octamer polymerization, whereas GTP promotes a compact, inactive conformation whose ability to polymerize is unknown. Also unclear is whether polymerization directly alters IMPDH catalytic activity. To address this, we identified point mutants of human IMPDH2 that either prevent or promote polymerization. Unexpectedly, we found that polymerized and non-assembled forms of recombinant IMPDH have comparable catalytic activity, substrate affinity, and GTP sensitivity and validated this finding in cells. Electron microscopy revealed that substrates and allosteric nucleotides shift the equilibrium between active and inactive conformations in both the octamer and the filament. Unlike other metabolic filaments, which selectively stabilize active or inactive conformations, recombinant IMPDH filaments accommodate multiple states. These conformational states are finely tuned by substrate availability and purine balance, while polymerization may allow cooperative transitions between states.
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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.