InterPro domain: IPR002082

Aspartate carbamoyltransferase (ATCase) catalyses the formation of carbamoyl-aspartate in the pyrimidine biosynthesis pathway, by the association of aspartate and carbamoyl-phosphate. This is the commitment step in the Escherichia coli pathway and is regulated by feedback inhibition by CTP, the final product of the pathway [ 1 ].

The structural organisation of the ATCase protein varies considerably between different organisms. In bacteria such as E. coli, Salmonella typhimurium andSerratia marcescens, the ATCase is a dodecamer of 2 catalytic (c) trimersand 3 regulatory (r) dimers. The catalytic domains are coded for by thepyrB gene [ 2 ], and the regulatory domains by pyrI [ 3 ]. In Gram-positive bacteriasuch as Bacillus subtilis, ATCase exists as a trimer of catalytic subunits, butunlike in E. coli, it neither contains nor binds to regulatory subunits. Ineukaryotes, ATCase is found as a single domain in a multifunctional enzymethat contains activity for glutamine amidotransferase, carbamoylphosphatesynthetase, dihydroorotase, and aspartate carbamoyltransferase.

1. The evolutionary history of the first three enzymes in pyrimidine biosynthesis. Bioessays 15, 157-64
2. Cloning and structure of the Bacillus subtilis aspartate transcarbamylase gene (pyrB). J. Biol. Chem. 261, 11156-65
3. In vivo formation of hybrid aspartate transcarbamoylases from native subunits of divergent members of the family Enterobacteriaceae. J. Bacteriol. 167, 285-90