ArticleeLife2020
Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 116 citations in OpenAlex.
- Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity.eLife · 2026Article
- Large-scale quaternary structural transitions underlie gain of function of SPOP cancer mutations.Molecular cell · 2026Article
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Inosine monophosphate dehydrogenases are key players for functional development in Arabidopsis.The Plant journal : for cell and molecular biology · 2026Article
- Review
- Structural basis of secreted acid phosphatase polymerization in the Leishmania parasite.Protein science : a publication of the Protein Society · 2026Article
- Structural basis for allosteric regulation of mycobacterial guanosine 5´-monophosphate reductase by ATP and GTP.Nature communications · 2026Article
- Rationally-Stabilized Inhibited State of IMPDH Proposes a Novel Targeting Approach Involving Its Cross-Domain and Assembly Suppression.Molecular biotechnology · 2026Article
- Expanding the targeted protein degradation approach with small molecule chimeras directed to the 26S proteasome.Nature communications · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Topical mycophenolate for the treatment of uveitis-associated inflammation.Journal of ophthalmic inflammation and infection · 2026Article
- 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
- IMPDH and GTP Metabolism in Cancer: Mechanisms, Regulation, and Translational Scope.Cancer science · 2025Review
- A Novel Allosteric Inhibitor Targeting IMPDH at Y233 Overcomes Resistance to Tyrosine Kinase Inhibitors in Lymphoma.Cancers · 2025Article
- Evolutionarily divergent Mycobacterium tuberculosis CTP synthase filaments are under selective pressure.Nature communications · 2025Article
- Y12C mutation disrupts IMPDH cytoophidia and alters cancer metabolism.The FEBS journal · 2025Article
- Entabolons: How Metabolites Modify the Biochemical Function of Proteins and Cause the Correlated Behavior of Proteins in Pathways.Journal of chemical information and modeling · 2025Review
- Purine Metabolism and Dystonia: Perspectives of a Long-Promised Relationship.Annals of neurology · 2025Review
- Depletion of nuclear cytoophidia in Alzheimer's disease.Free neuropathology · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. IMPDH reversibly polymerizes in cells and tissues in response to changes in metabolic demand. Self-assembly of metabolic enzymes is increasingly recognized as a general mechanism for regulating activity, typically by stabilizing specific conformations of an enzyme, but the regulatory role of IMPDH filaments has remained unclear. Here, we report a series of human IMPDH2 cryo-EM structures in both active and inactive conformations. The structures define the mechanism of filament assembly, and reveal how filament-dependent allosteric regulation of IMPDH2 makes the enzyme less sensitive to feedback inhibition, explaining why assembly occurs under physiological conditions that require expansion of guanine nucleotide pools. Tuning sensitivity to an allosteric inhibitor distinguishes IMPDH from other metabolic filaments, and highlights the diversity of regulatory outcomes that can emerge from self-assembly.
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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.