Disease relevance of pyrC

• Nucleotide sequence and expression of the pyrC gene of Escherichia coli K-12 [1].
• Cloning, sequencing, and characterizing the Lactobacillus leichmannii pyrC gene encoding dihydroorotase [2].
• In Thermus strain ZO5, pyrB and pyrC gene expression is repressed three- to fourfold by uracil and increased twofold by arginine [3].
• Aspartate transcarbamoylase genes of Pseudomonas putida: requirement for an inactive dihydroorotase for assembly into the dodecameric holoenzyme [4].

High impact information on pyrC

• Mammalian dihydroorotase: nucleotide sequence, peptide sequences, and evolution of the dihydroorotase domain of the multifunctional protein CAD [5].
• Mass spectrometric determination of the cleavage sites in Escherichia coli dihydroorotase induced by a cysteine-specific reagent [6].
• Glutamine-dependent carbamyl-phosphate synthetase (CPSase), aspartate transcarbamylase, and dihydroorotase activities are carried by a 243-kDa polypeptide chain that is organized into discrete functional domains connected by interdomain linkers [7].
• Dihydroorotase from Escherichia coli. Substitution of Co(II) for the active site Zn(II) [8].
• Escherichia coli dihydroorotase has been crystallized in the presence of the product, L-dihydroorotate (L-DHO), and the structure refined at 1.9A resolution [9].

Chemical compound and disease context of pyrC

• The pyrC gene of Escherichia coli K-12, which encodes the pyrimidine biosynthetic enzyme dihydroorotase, was cloned as part of a 1.6-kilobase-pair chromosomal fragment [1].

Biological context of pyrC

• An open reading frame encoding a 348-amino acid polypeptide (Mr = 38,827) was identified as the pyrC structural gene by comparing the amino acid composition predicted from the DNA sequence with that previously determined for the dihydroorotase subunit [1].
• Transcriptional initiation was shown to occur within a region located 36 to 39 base pairs upstream of the pyrC structural gene [1].
• Nuclease Bal31-deletion derivatives of pyrC plasmids indicate that this gene does not affect the expression of pyrC [10].
• Mutational analysis of this regulatory region showed that the formation of a hairpin at the 5' end of the pyrC transcript, which overlaps the pyrC ribosome binding site, is required for repression of pyrC expression [11].
• To define the mechanism of this regulation, an essential regulatory region between the pyrC promoter and the initial codons of the pyrC structural gene was identified [11].

Associations of pyrC with chemical compounds

• The level of pyrC transcription and dihydroorotase synthesis was coordinately derepressed by pyrimidine limitation, indicating that regulation occurs, at least primarily, at the transcriptional level [1].
• Treatment of NEM-blocked dihydroorotase ((NEM)dihydroorotase) with the chelator 2,6-pyridinedicarboxylic acid at pH 5.0 in the absence of oxygen and trace metal ions removes the active site Zn(II) with a half-life of 15 min, allowing the production of milligram amounts of moderately stable apo-(NEM)dihydroorotase in about 80% yield [8].
• Dihydroorotase plays a key role in pyrimidine biosynthesis by catalyzing the reversible interconversion of carbamoyl aspartate to dihydroorotate [12].
• Function of conserved histidine residues in mammalian dihydroorotase [13].
• The activities of both isomers of 5 as inhibitors of mammalian dihydroorotase were marginally greater than that of the parent phosphinic acid 4, indicating a weak binding enhancement due to the phosphinothioic acid moiety [14].

Other interactions of pyrC

• A superfamily of cyclic amidohydrolases, including dihydropyrimidinase, allantoinase, hydantoinase, and dihydroorotase, all of which are involved in the metabolism of purine and pyrimidine rings, was recently proposed based on the rigidly conserved structural domains in identical positions of the related enzymes [15].

Analytical, diagnostic and therapeutic context of pyrC

• Results from gel filtration of dihydroorotase cyanylated on the two cysteines indicate that these residues are involved in subunit interactions leading to the active dimer [6].
• Crystallization of hamster dihydroorotase: involvement of a disulfide-linked tetrameric form [16].
• Assay of Escherichia coli dihydroorotase with enantiomeric substrate: practical preparation of carbamyl L-aspartate and high-performance liquid chromatography analysis of catalysis product [17].

References