ArticleScientific reports2016
Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Molecular mechanisms and therapeutic potential of tryptophan metabolism in gut-brain signaling transduction: a narrative review.Journal of neuroinflammation · 2026Review
- Decoding atherosclerosis through lactylation: multi-omics integration with experimental validation.Frontiers in cell and developmental biology · 2026Article
- Protein oxidation, glycation, and carbamylation in patients with adrenal masses.Frontiers in molecular biosciences · 2026Article
- Hepatic tryptophan metabolism links chronic stress to liver cancer.Nature metabolism · 2026Article
- Quinolinic acid metabolism may mitigate AKI to CKD transition.bioRxiv : the preprint server for biology · 2025Article
- Enzymatic approaches to nicotinic acid synthesis: recent advances and future prospects.Frontiers in bioengineering and biotechnology · 2025Review
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- Structure, mechanism and inhibition of anthranilate phosphoribosyltransferase.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Review
- Roles of NADInternational journal of molecular sciences · 2022Review
- NADAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Review
- Multienvironment QTL analysis delineates a major locus associated with homoeologous exchanges for water-use efficiency and seed yield in canola.Plant, cell & environment · 2022Article
- QPRT Acts as an Independent Prognostic Factor in Invasive Breast Cancer.Journal of oncology · 2022Article
- NAD metabolism in aging and cancer.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- NADSignal transduction and targeted therapy · 2020Review
- Article
- Targeting NADMolecular cancer research : MCR · 2020Article
- Analysis of the uterine lumen in fertility-classified heifers: II. Proteins and metabolites†.Biology of reproduction · 2020Article
- Macrophage de novo NADNature immunology · 2019Article
- Major Developments in the Design of Inhibitors along the Kynurenine Pathway.Current medicinal chemistry · 2017Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quinolinate phosphoribosyltransferase (QPRT) catalyses the production of nicotinic acid mononucleotide, a precursor of de novo biosynthesis of the ubiquitous coenzyme nicotinamide adenine dinucleotide. QPRT is also essential for maintaining the homeostasis of quinolinic acid in the brain, a possible neurotoxin causing various neurodegenerative diseases. Although QPRT has been extensively analysed, the molecular basis of the reaction catalysed by human QPRT remains unclear. Here, we present the crystal structures of hexameric human QPRT in the apo form and its complexes with reactant or product. We found that the interaction between dimeric subunits was dramatically altered during the reaction process by conformational changes of two flexible loops in the active site at the dimer-dimer interface. In addition, the N-terminal short helix α1 was identified as a critical hexamer stabilizer. The structural features, size distribution, heat aggregation and ITC studies of the full-length enzyme and the enzyme lacking helix α1 strongly suggest that human QPRT acts as a hexamer for cooperative reactant binding via three dimeric subunits and maintaining stability. Based on our comparison of human QPRT structures in the apo and complex forms, we propose a drug design strategy targeting malignant glioma.
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Registered trials
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