The evolutionary history of the first three enzymes in pyrimidine biosynthesis

@article{Davidson1993TheEH,
  title={The evolutionary history of the first three enzymes in pyrimidine biosynthesis},
  author={Jeffrey N. Davidson and K. C. Chen and R S Jamison and L A Musmanno and Christine B Kern},
  journal={BioEssays},
  year={1993},
  volume={15}
}
Some metabolic pathways are nearly ubiquitous among organisms: the genes encoding the enzymes for such pathways must therefore be ancient and essential. De novo pyrimidine biosynthesis is an example of one such metabolic pathway. In animals a single protein called CAD Abbreviations: CAD, trifunctional protein catalyzing the first three steps of de novo pyrimidine biosynthesis in higher eukaryotes; CPS, carbamyl phosphate synthetase domain; CPSase, carbamyl phosphate synthetase activity; ATC… Expand
View on Wiley
ncbi.nlm.nih.gov
82 Citations
Background Citations
22
Methods Citations
1

82 Citations

Citation Type

Citation Type

Evolutionary implications of the mosaic pyrimidine-biosynthetic pathway in eukaryotes.
TLDR
The phylogenetic analyses of DHOD and OMPDC support the implications of the mosaic pyrimidine biosynthetic pathway in eukaryotes and the potential importance of the horizontal gene transfer(s) and endosymbiosis in establishing the mosaic pathway is discussed. Expand
CAD: A Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis
TLDR
A model of CAD is proposed that sets the DHO and ATC domains as the central framework of the hexameric particles and is expected to be similar to the Escherichia coli CPS and human mitochondrial CPS1 crystal structures. Expand
Structural and transcriptional analysis of the pyrABCN, pyrD and pyrF genes in Aspergillus nidulans and the evolutionary origin of fungal dihydroorotases
TLDR
Cl cloning, mapping and transcriptional characterization of some pyrimidine biosynthesis genes in the filamentous fungus Aspergillus nidulans are reported and Comparison of amino acid sequences of active dihydroorotases with related enzymes and with their non‐functional homologues in yeast and As pergillus indicates that the active diHydro orotases from fungi are more similar to ureases and enzymes of the pyridine degradation pathway. Expand
CAD, A Multienzymatic Protein at the Head of de Novo Pyrimidine Biosynthesis.
TLDR
Some of the most significant efforts to decipher the architecture of CAD and to understand its catalytic and regulatory mechanisms are retrace. Expand
Phylogenetic analysis of carbamoylphosphate synthetase genes: complex evolutionary history includes an internal duplication within a gene which can root the tree of life.
TLDR
It is confirmed that internal similarity within the synthetase domain of CPS is the result of an ancient gene duplication that preceded the divergence of the Bacteria, Archaea, and Eukarya, and used in phylogenetic tree construction to root the tree of life. Expand
Half of Saccharomyces cerevisiae Carbamoyl Phosphate Synthetase Produces and Channels Carbamoyl Phosphate to the Fused Aspartate Transcarbamoylase Domain*
TLDR
The overall CPSase-ATCase reaction is much less sensitive than the parent molecule to the ATCase bisubstrate analogue,N-phosphonacetyl-l-aspartate (PALA), providing evidence that the endogenously produced carbamoyl phosphate is sequestered and channeled to theATCase active site. Expand
Molecular evolution of the histidine biosynthetic pathway
TLDR
Evidence that the hisA and the hisF genes and their homologues are the result of two successive duplication events that apparently took place before the separation of the three cellular lineages is extended supports the idea that during the early stages of metabolic evolution at least parts of the histidine biosynthetic pathway were mediated by enzymes of broader substrate specificities. Expand
Deciphering CAD: Structure and function of a mega‐enzymatic pyrimidine factory in health and disease
TLDR
This review summarizes significant progress over the past 10 years towards the characterization of CAD's architecture, function, regulatory mechanisms and cellular compartmentalization, as well as the recent finding of a new and rare neurometabolic disorder caused by defects in CAD activities. Expand
Organisation and sequence determination of glutamine-dependent carbamoyl phosphate synthetase II in Toxoplasma gondii.
TLDR
The novel C-terminal regulatory domain may explain the lack of activation of Toxoplasma gondii carbamoyl phosphate synthetase II by the allosteric effector 5-phosphoribosyl 1-pyrophosphate. Expand
De novo synthesis of pyrimidine nucleotides; emerging interfaces with signal transduction pathways
TLDR
Recent studies demonstrate that CAD, a rate-limiting enzyme in the de novo synthesis of pyrimidines, is regulated through reversible phosphorylation, Myc-dependent transcriptional changes and caspase-mediated degradation, and point to increasing evidence for cooperation between key cell signaling pathways and basic elements of cellular metabolism. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 43 REFERENCES
Pyrimidine biosynthesis in Saccharomyces cerevisiae: the ura2 cluster gene, its multifunctional enzyme product, and other structural or regulatory genes involved in de novo UMP synthesis.
  • M. Denis-Duphil
  • Biology, Medicine
  • Biochemistry and cell biology = Biochimie et biologie cellulaire
  • 1989
TLDR
Channeling of carbamyl phosphate, the first intermediate in the pathway, has been demonstrated both in vitro and in permeabilized cells, and aTCase activity of both wild-type and protease-deficient strains has been found to be localized in the nucleus. Expand
Synthesis of the nonconserved dihydroorotase domain of the multifunctional hamster CAD protein in Escherichia coli.
TLDR
A 'genetic cassette', containing information for neither the CPSase nor the ATCase domain, can direct the synthesis of a polypeptide with DHOase activity. Expand
Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD.
TLDR
Analysis of the nucleotide and amino acid sequence identities among the various carbamyl phosphate synthetases suggests that the gene fusion which joined the GLN and CPS domains was an early event in the evolution of eukaryotic organisms and that the Saccharomyces cerevisiae enzyme consisting of separate subunits arose by defusion from an ancestral multifunctional protein. Expand
Complete hamster CAD protein and the carbamylphosphate synthetase domain of CAD complement mammalian cell mutants defective in de novo pyrimidine biosynthesis
TLDR
A derivative construct of theCAD cDNA was generated that should encode only the CPSase domain and a protein was synthesized that had significant CPSase activity both in vivo and in vitro. Expand
Functional organization and nucleotide sequence of the Bacillus subtilis pyrimidine biosynthetic operon.
TLDR
A 12.5-kilobase segment of Bacillus subtilis chromosomal DNA containing the entire pyrimidine biosynthetic (pyr) gene cluster has been cloned and sequenced and a transcription terminator was detected in this region that reduced but did not fully block transcriptional readthrough. Expand
Controlled proteolysis of the multifunctional protein that initiates pyrimidine biosynthesis in mammalian cells: evidence for discrete structural domains.
  • M. Mally, D. Grayson, D. Evans
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1981
TLDR
Kinetic studies of the controlled proteolysis of the molecule by elastase showed that the protein was not attacked at random by the protease but rather was successively cleaved into at least six well-defined proteolytic fragments, showing that this multifunctional protein is organized as discrete structural domains in which regions of the polypeptide chain are autonomously folded into separate functional units. Expand
In situ behavior of the pyrimidine pathway enzymes in Saccharomyces cerevisiae. 2. Reaction mechanism of aspartate transcarbamylase dissociated from carbamylphosphate synthetase by genetic alteration.
TLDR
The reaction mechanism of Saccharomyces cerevisiae aspartate transcarbamylase was studied in permeabilized cells of a mutant in which this enzyme is not associated to carbamylphosphate synthetase, which indicates that the association of the two enzymes within the multienzymatic complex alters the apparent kinetic properties of this enzyme. Expand
Studies on channeling of carbamoyl-phosphate in the multienzyme complex that initiates pyrimidine biosynthesis in rat ascites hepatoma cells.
TLDR
Results indicate that carbamoyl-phosphate can be channeled in the multienzyme complex of AH 13 cells, but the extent of channeling is very small, contrary to expectation. Expand
Sequence of the small subunit of yeast carbamyl phosphate synthetase and identification of its catalytic domain.
TLDR
A 13-amino acid long sequence is proposed to be part of the catalytic domain of this class of enzymes, based on the observed homologies in the primary sequences of the other amidotransferases examined. Expand
Alteration in structure of multifunctional protein from Chinese hamster ovary cells defective in pyrimidine biosynthesis.
  • J. Davidson, D. Patterson
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1979
TLDR
A combined genetic, biochemical, and immunological approach has clarified structural relationships involving the first three enzymes of de novo pyrimidine biosynthesis and concluded that these three enzymes reside in a single multifunctional 220,000-dalton polypeptide. Expand
...
1
2
3
4
5
...