Integrated allosteric regulation in the S. cerevisiae carbamylphosphate synthetase - aspartate transcarbamylase multifunctional protein.

Background: The S. cerevisiae carbamylphosphate synthetase - aspartate transcarbamylase multifunctional protein catalyses the first two reactions of the pyrimidine pathway. In this organism, these two reactions are feedback inhibited by the end product UTP.

Design, synthesis and activity of bisubstrate, transition-state analogues and competitive inhibitors of aspartate transcarbamylase.

Aspartate transcarbamylase initiates the de novo biosynthetic pathway for the production of the pyrimidine nucleotides, precursors of nucleic acids. This pathway is particularly active in rapidly growing cells and tissues. Thus, this enzyme has been tested as a potential target for antiproliferative drugs.