|PROSITE documentation PDOC00401|
Dihydroorotase (EC 18.104.22.168) (DHOase) catalyzes the third step in the de novo biosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion which is required for its catalytic activity .
In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC). In higher eukaryotes, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis . The DHOase domain is located in the central part of this polyprotein. In yeasts, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain  is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.
The comparison of DHOase sequences from various sources shows  that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested  to be involved in binding the zinc ion. The second is found in the C-terminal part. We developed signature patterns for both regions.
Allantoinase (EC 22.214.171.124) is the enzyme that hydrolyzes allantoin into allantoate. In yeast (gene DAL1) , it is the first enzyme in the allantoin degradation pathway; in amphibians  and fishs it catalyzes the second step in the degradation of uric acid. The sequence of allantoinase is evolutionary related to that of DHOases.Last update:
December 2004 / Pattern and text revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Brown D.C. Collins K.D.|
|Title||Dihydroorotase from Escherichia coli. Substitution of Co(II) for the active site Zn(II).|
|Source||J. Biol. Chem. 266:1597-1604(1991).|
|2||Authors||Davidson J.N. Chen K.C. Jamison R.S. Musmanno L.A. Kern C.B.|
|Title||The evolutionary history of the first three enzymes in pyrimidine biosynthesis.|
|3||Authors||Souciet J.-L. Nagy M. Le Gouar M. Lacroute F. Potier S.|
|Title||Organization of the yeast URA2 gene: identification of a defective dihydroorotase-like domain in the multifunctional carbamoylphosphate synthetase-aspartate transcarbamylase complex.|
|4||Authors||Guyonvarch A. Nguyen-Juilleret M. Hubert J.-C. Lacroute F.|
|Title||Structure of the Saccharomyces cerevisiae URA4 gene encoding dihydroorotase.|
|Source||Mol. Gen. Genet. 212:134-141(1988).|
|5||Authors||Buckholz R.G. Cooper T.G.|
|Title||The allantoinase (DAL1) gene of Saccharomyces cerevisiae.|
|6||Authors||Hayashi S. Jain S. Chu R. Alvares K. Xu B. Erfurth F. Usuda N. Rao M.S. Reddy S.K. Noguchi T.|
|Title||Amphibian allantoinase. Molecular cloning, tissue distribution, and functional expression.|
|Source||J. Biol. Chem. 269:12269-12276(1994).|