Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
1994-10-11
pubmed:databankReference
pubmed:abstractText
The pig and human dihydropyrimidine dehydrogenase (DPD) cDNAs were cloned and sequenced. The pig enzyme, expressed in Escherichia coli, catalyzed the reduction of uracil, thymine, and 5-fluorouracil with kinetics approximating those published for the enzyme purified from mammalian liver. DPD could be expressed in significant quantities only when uracil was added to the bacterial growth medium. The pig and human enzymes contained 1025 amino acids and calculated M(r) = 111,416 and 111,398, respectively. Conserved domains corresponding to a possible NADPH binding site and FAD binding site were found in the NH2-terminal half of the proteins and two motifs of putative [4Fe-4S] binding sites were found near to the carboxyl terminus of the enzyme. The latter corresponds to the labile COOH-terminal fragment previously shown to contain the iron sulfur centers. A sequence encompassing a peptide corresponding to the uracil binding site was found between the NADPH/FAD-containing NH2-terminal portion of the protein and the iron-sulfur binding sites near to the COOH terminus. Thus, the DPD appears to be derived from at least three distinct domains. The DPYD gene was localized to the centromeric region of human chromosome 1 between 1p22 and q21.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
269
pubmed:geneSymbol
DPD, DPYD
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23192-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8083224-Amino Acid Sequence, pubmed-meshheading:8083224-Animals, pubmed-meshheading:8083224-Base Sequence, pubmed-meshheading:8083224-Chromosome Mapping, pubmed-meshheading:8083224-Chromosomes, Human, Pair 1, pubmed-meshheading:8083224-Cricetinae, pubmed-meshheading:8083224-DNA, Complementary, pubmed-meshheading:8083224-Dihydrouracil Dehydrogenase (NADP), pubmed-meshheading:8083224-Fluorouracil, pubmed-meshheading:8083224-Humans, pubmed-meshheading:8083224-Hybrid Cells, pubmed-meshheading:8083224-Metabolism, Inborn Errors, pubmed-meshheading:8083224-Mice, pubmed-meshheading:8083224-Molecular Sequence Data, pubmed-meshheading:8083224-Oxidoreductases, pubmed-meshheading:8083224-Recombinant Proteins, pubmed-meshheading:8083224-Swine, pubmed-meshheading:8083224-Thymine, pubmed-meshheading:8083224-Uracil
pubmed:year
1994
pubmed:articleTitle
cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria.
pubmed:affiliation
Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article