ArticleThe EMBO journal2001
Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 137 citations in OpenAlex.
- Genetic Variants Associated with Fluoropyrimidine-Induced Toxicity in Real-World Patients After Pre-EmptivePharmaceuticals (Basel, Switzerland) · 2026Article
- Functional studies of human variants in C. elegans link iron metabolism to DPD deficiency and 5-FU sensitivity.Genetics · 2026Article
- Article
- Exploring a unique class of flavoenzymes: Identification and biochemical characterization of ribosomal RNA dihydrouridine synthase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Binding Pattern and Structural Interactome of the Anticancer Drug 5-Fluorouracil: A Critical Review.International journal of molecular sciences · 2024Review
- Fluoropyrimidine Toxicity: the Hidden Secrets of DPYD.Current drug metabolism · 2024Review
- New Insights into rice pyrimidine catabolic enzymes.Frontiers in plant science · 2023Article
- Evolutionary Diversity of Dus2 Enzymes Reveals Novel Structural and Functional Features among Members of the RNA Dihydrouridine Synthases Family.Biomolecules · 2022Article
- Identification of fungal dihydrouracil-oxidase genes by expression in Saccharomyces cerevisiae.Antonie van Leeuwenhoek · 2022Article
- Importance of RareFrontiers in pharmacology · 2022Article
- Optimization of the precursor supply for an enhanced FK506 production inFrontiers in bioengineering and biotechnology · 2022Article
- Article
- Force Field Parameters for FeMolecules (Basel, Switzerland) · 2021Article
- Iron-sulfur flavoenzymes: the added value of making the most ancient redox cofactors and the versatile flavins work together.Open biology · 2021Article
- Drug-metabolizing enzymes: role in drug resistance in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- A ferredoxin-dependent dihydropyrimidine dehydrogenase in Clostridium chromiireducens.Bioscience reports · 2020Article
- In Vitro Assessment of Fluoropyrimidine-Metabolizing Enzymes: Dihydropyrimidine Dehydrogenase, Dihydropyrimidinase, and β-Ureidopropionase.Journal of clinical medicine · 2020Review
- New DPYD variants causing DPD deficiency in patients treated with fluoropyrimidine.Cancer chemotherapy and pharmacology · 2020Article
- Rare Dihydropyrimidine Dehydrogenase Variants and Toxicity by Floropyrimidines: A Case Report.Frontiers in oncology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dihydropyrimidine dehydrogenase catalyzes the first step in pyrimidine degradation: the NADPH-dependent reduction of uracil and thymine to the corresponding 5,6-dihydropyrimidines. Its controlled inhibition has become an adjunct target for cancer therapy, since the enzyme is also responsible for the rapid breakdown of the chemotherapeutic drug 5-fluorouracil. The crystal structure of the homodimeric pig liver enzyme (2x 111 kDa) determined at 1.9 A resolution reveals a highly modular subunit organization, consisting of five domains with different folds. Dihydropyrimidine dehydrogenase contains two FAD, two FMN and eight [4Fe-4S] clusters, arranged in two electron transfer chains that pass the dimer interface twice. Two of the Fe-S clusters show a hitherto unobserved coordination involving a glutamine residue. The ternary complex of an inactive mutant of the enzyme with bound NADPH and 5-fluorouracil reveals the architecture of the substrate-binding sites and residues responsible for recognition and binding of the drug.
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