Mutagenesis Studies of Conserved Residues in Mammalian Dihydroorotase
Dihydroorotase (DHOase3) (L-5, 6-dihydroorotate amidohydrolase, EC 220.127.116.11) catalyzes the reversible cyclization of carbamyl aspartate to form dihydroorotate, the third step in de novo pyrimidine biosynthesis. In mammals, the activity is carried by the multifunctional protein CAD, which also carries the activities of the first two steps in the pathway, carbamyl phosphate synthetase (CPSase) and aspartate transcarbamylase (ATCase). The hamster CAD molecule is a hexamer consisting of six identical Polypeptides, each having a molecular weight of 242 kDa. Limited proteolysis and sequence analysis have shown that the DHOase activity is associated with a discrete domain of the protein (Kelly et al., 1986; Simmer et al., 1990).
KeywordsLimited Proteolysis Mutant D1512N Pyrimidine Biosynthesis Carbamyl Phosphate Reversible Cyclization
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