ArticleNature communications2015
Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 102 citations in OpenAlex.
- Three phosphatase families form a community: The phosphohydrolases that act upon inositol pyrophosphates.FEBS letters · 2026Review
- Inosine monophosphate dehydrogenases are key players for functional development in Arabidopsis.The Plant journal : for cell and molecular biology · 2026Article
- Disease progression in IMPDH1 gene-associated rod-cone dystrophy caused by a rare p.Thr244Pro heterozygous variant.Documenta ophthalmologica. Advances in ophthalmology · 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
- 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
- Retinopathy-associated inosine monophosphate dehydrogenase 1 mutations cause metabolic and filament defects in cones.Disease models & mechanisms · 2025Article
- Y12C mutation disrupts IMPDH cytoophidia and alters cancer metabolism.The FEBS journal · 2025Article
- IMPDH2's Central Role in Cellular Growth and Diseases: A Potential Therapeutic Target.Cell proliferation · 2025Review
- Purine Metabolism and Dystonia: Perspectives of a Long-Promised Relationship.Annals of neurology · 2025Review
- IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency.EMBO reports · 2024Article
- Deciphering the allosteric regulation of mycobacterial inosine-5'-monophosphate dehydrogenase.Nature communications · 2024Article
- Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule.Nature communications · 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
- Insights on the conformation and appropriate drug-target sites on retinal IMPDH1 using the 604-aa isoform lacking the C-terminal extension.Research in pharmaceutical sciences · 2023Article
- Neurodevelopmental disorder mutations in the purine biosynthetic enzyme IMPDH2 disrupt its allosteric regulation.The Journal of biological chemistry · 2023Article
- 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
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inosine-5'-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches.
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