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 Kuey Chu Chen and Robert S. Jamison and Lisa 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…
82 Citations
Evolutionary implications of the mosaic pyrimidine-biosynthetic pathway in eukaryotes.
- BiologyGene
- 2000
Structural and transcriptional analysis of the pyrABCN, pyrD and pyrF genes in Aspergillus nidulans and the evolutionary origin of fungal dihydroorotases
- BiologyMolecular microbiology
- 1999
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.
CAD, A Multienzymatic Protein at the Head of de Novo Pyrimidine Biosynthesis.
- BiologySub-cellular biochemistry
- 2019
Some of the most significant efforts to decipher the architecture of CAD and to understand its catalytic and regulatory mechanisms are retrace.
Phylogenetic analysis of carbamoylphosphate synthetase genes: complex evolutionary history includes an internal duplication within a gene which can root the tree of life.
- BiologyMolecular biology and evolution
- 1996
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.
Half of Saccharomyces cerevisiae Carbamoyl Phosphate Synthetase Produces and Channels Carbamoyl Phosphate to the Fused Aspartate Transcarbamoylase Domain*
- Biology, ChemistryThe Journal of Biological Chemistry
- 1999
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.
Molecular evolution of the histidine biosynthetic pathway
- BiologyJournal of Molecular Evolution
- 2004
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.
Deciphering CAD: Structure and function of a mega‐enzymatic pyrimidine factory in health and disease
- BiologyProtein science : a publication of the Protein Society
- 2021
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.
Organisation and sequence determination of glutamine-dependent carbamoyl phosphate synthetase II in Toxoplasma gondii.
- Biology, ChemistryInternational journal for parasitology
- 2003
De novo synthesis of pyrimidine nucleotides; emerging interfaces with signal transduction pathways
- Biology, ChemistryCellular and Molecular Life Sciences CMLS
- 2003
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.
As in Saccharomyces cerevisiae, aspartate transcarbamoylase is assembled on a multifunctional protein including a dihydroorotase-like cryptic domain in Schizosaccharomyces pombe
- BiologyCurrent Genetics
- 2004
Genetic investigations confirmed that both GLNase/CPSase and ATCase activities are carried out by the same polypeptide and are also both feedback-inhibited by UTP (uridine triphosphate).
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