Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil

EMBO Journal

Volumn 20, Issue 4, 2001, Pages 650-660

  Dobritzsch, Doreen ^a   Schneider, Gunter ^a   Schnackerz, Klaus D ^b,c   Lindqvist, Ylva ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b UNIVERSITY OF WÜRZBURG   (Germany)

^c UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

Electron transfer; Flavin; Iron sulfur clusters; Protein crystallography; Pyrimidine metabolism

Indexed keywords

DIHYDROPYRIMIDINE DEHYDROGENASE; FLAVINE ADENINE NUCLEOTIDE; FLAVINE MONONUCLEOTIDE; FLUOROURACIL; IRON; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SULFUR; THYMINE; URACIL;

ARTICLE; CANCER THERAPY; CATALYSIS; CRYSTAL STRUCTURE; DRUG METABOLISM; DRUG PROTEIN BINDING; ENZYME STRUCTURE; ENZYME SUBSTRATE COMPLEX; ENZYME SUBUNIT; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; RESPIRATORY CHAIN;

SUS SCROFA;

EID: 0035865277     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1093/emboj/20.4.650     Document Type: Article

References (47)

1. Eniluracil treatment completely inactivates dihydropyrimidine dehydrogenase in colorectal tumors
2. cDNA cloning of bovine liver dihydropyrimidine dehydrogenase
3. Fluoropyrimidines: A critical evaluation
4. Crystallography & NMR system: A new software suite for macromolecular structure determination
5. Structure, function and evolution of bacterial ferredoxins
6. Crystal structure of the key anaerobic enzyme pyruvate: Ferredoxin oxidoreductase, free and in complex with pyruvate
7. The CCP4 suite: Programs for protein crystallography
8. Phase combination and cross validation in iterated density modification calculations
9. Maximum-likelihood heavy-atom parameter refinement in the MIR and MAD methods
10. Crystallization and preliminary X-ray study of pig liver dihydropyrimidine dehydrogenase
11. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities
12. On the iron-sulfur clusters in the complex redox enzyme dihydropyrimidine dehydrogenase
13. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma
14. Distribution and inhibition of dihydrouracil dehydrogenase activities in human tissues using 5-fluorouracil as a substrate
15. 19F nuclear magnetic resonance spectroscopy, for patients receiving chemotherapy with and without methotrexate pretreatment
16. Structure of the Escherichia coli fumarate reductase respiratory complex
17. Improved methods for building protein models in electron density maps and the location of errors in these models
18. Substrate binding and catalysis by glutathione reductase as derived from refined enzyme: Substrate crystal structures at 2 Å resolution
19. Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity
20. MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures
21. PROCHECK: A program to check the stereochemical quality of protein structures
22. Twist in catalysis: Alternating conformations of Escherichia coli thioredoxin reductase
23. A WWW service system for automatic comparison of protein structures
24. FINDNCS: A program to detect non-crystallographic symmetries in protein crystals from heavy-atom sites
25. Purification and characterization of dihydropyrimidine dehydrogenase from human liver
26. Multicenter phase II study to evaluate a 28-day regimen of oral fluorouracil plus eniluracil in the treatment of patients with previously untreated metastatic colorectal cancer
27. Raster3D: Photorealistic molecular graphics
28. Dihydropyrimidine dehydrogenase (DPD) and clinical pharmacology of 5-fluorouracil
29. Structure-activity relationship of ligands of dihydrouracil dehydrogenase from mouse liver
30. Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons
31. Processing of X-ray diffraction data collected in oscillation mode
32. Natural engineering principles of electron tunneling in biological oxidation-reduction
33. The use of thymidylate synthase inhibitors in the treatment of advanced colorectal cancer: Current status
34. Purification and characterization of dihydropyrimidine dehydrogenase from pig liver
35. Kinetic mechanism of dihydropyrimidine dehydrogenase from pig liver
36. Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil
37. Mutations at codon 974 of the DPYD gene are a rare event
38. Purification, characterization, and kinetics of porcine recombinant dihydropyrimidine dehydrogenase
39. Porcine recombinant dihydropyrimidine dehydrogenase: Comparison of the spectroscopic and catalytic properties of the wild-type and the C671A mutant enzymes
40. The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function
41. Gene duplication in glutathione reductase
42. Purification and properties of dihydrothymine dehydrogenase from rat liver
43. Automated structure solution for MIR and MAD
44. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase defiency
45. Degradation of pyrimidines and pyrimidine analogs - Pathways and mutual influences
46. cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria
47. + and NADPH suggesting a mechanism for the electron transfer of an enzyme family