Aspartate transcarbamoylase (ATCase)

Aspartate transcarbamoylase is a multi-subunit, allosteric enzyme that executes the first committed and rate-limiting step in pyrimidine nucleotide biosynthesis. It consists of catalytic and regulatory subunits, forming a dodecameric holoenzyme in bacteria, with a similar domain arrangement in humans (where ATCase activity is part of the larger CAD multienzyme complex)[1][7][9]. The enzyme is regulated through feedback inhibition by CTP and activation by ATP, linking nucleotide synthesis to cellular needs[1][3][5][7]. Structurally, it exists predominantly in two states: a low-activity T (tense) state and a high-activity R (relaxed) state, transitions between which are governed by substrate and effector binding[2][7][10]. ATCase is a well-validated drug target for infections, cancer, and other proliferative disorders, with several small molecule inhibitors under clinical and preclinical investigation[2][8][9][10].

Other names

Aspartate carbamoyltransferaseATCase

Inhibition of ATCase blocks de novo pyrimidine biosynthesis, depriving cells of nucleotide precursors; many inhibitors are allosteric and stabilize the enzyme in its inactive T (tense) state