InterPro domain: IPR006132

This entry contains two related enzymes:

1. Aspartate carbamoyltransferase ( 2.1.3.2 ) (ATCase) catalyzes the conversionof aspartate and carbamoyl phosphate to carbamoylaspartate, the second stepin the de novo biosynthesis of pyrimidine nucleotides [ 1 ]. In prokaryotesATCase consists of two subunits: a catalytic chain (gene pyrB) and aregulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi-functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CADin mammals [ 2 ]) that also catalyzes other steps of the biosynthesis ofpyrimidines.
2. Ornithine carbamoyltransferase ( 2.1.3.3 ) (OTCase) catalyzes the conversionof ornithine and carbamoyl phosphate to citrulline. In mammals this enzymeparticipates in the urea cycle [ 3 ] and is located in the mitochondrialmatrix. In prokaryotes and eukaryotic microorganisms it is involved in thebiosynthesis of arginine. In some bacterial species it is also involved in thedegradation of arginine [ 4 ] (the arginine deaminase pathway).

It has been shown [ 5 ] that these two enzymes are evolutionary related. Thepredicted secondary structure of both enzymes are similar and there are someregions of sequence similarities. One of these regions includes threeresidues which have been shown, by crystallographic studies [ 6 ], to beimplicated in binding the phosphoryl group of carbamoyl phosphate and may also play a role in trimerization of the molecules [ 7 ]. The carboxyl-terminal, aspartate/ornithine-binding domain is is described by IPR006131 .

1. Cloning and structure of the Bacillus subtilis aspartate transcarbamylase gene (pyrB). J. Biol. Chem. 261, 11156-65
2. The evolutionary history of the first three enzymes in pyrimidine biosynthesis. Bioessays 15, 157-64
3. Evolutionary aspects of urea cycle enzyme genes. Bioessays 10, 163-6
4. Primary and quaternary structure of the catabolic ornithine carbamoyltransferase from Pseudomonas aeruginosa. Extensive sequence homology with the anabolic ornithine carbamoyltransferases of Escherichia coli. Eur. J. Biochem. 166, 111-7
5. Protein differentiation: a comparison of aspartate transcarbamoylase and ornithine transcarbamoylase from Escherichia coli K-12. Proc. Natl. Acad. Sci. U.S.A. 81, 4864-8
6. Structure of unligated aspartate carbamoyltransferase of Escherichia coli at 2.6-A resolution. Proc. Natl. Acad. Sci. U.S.A. 81, 4037-40
7. Assessment of the allosteric mechanism of aspartate transcarbamoylase based on the crystalline structure of the unregulated catalytic subunit. Proc. Natl. Acad. Sci. U.S.A. 96, 5388-93