Aspartate kinase (AK)

Aspartate kinase is an enzyme that catalyzes the phosphorylation of L-aspartate to 4-phospho-L-aspartate using ATP, representing the first committed and rate-limiting step in the biosynthesis of the aspartate family of amino acids: lysine, threonine, methionine, and isoleucine[1][2][4][7]. This enzyme is tightly regulated by feedback inhibition from its metabolic end-products, especially lysine and threonine, which bind to regulatory ACT domains in a manner dependent on species and isoform[1][2][3][5][8]. Aspartate kinase exists as different oligomeric assemblies (homooligomer or heterotetramer) and contains both catalytic and regulatory domains[2][3][5]. AK is found exclusively in microorganisms and plants, not in animals—hence, it is absent from humans and other mammals[7]. Inhibition of aspartate kinase is of commercial and agricultural interest: it is a target in the development of herbicides and antibiotics, as animals rely on dietary supply of aspartate-family amino acids whereas many pathogens and weeds must synthesize them[7]. Its absence from humans reduces concerns for direct toxicity from drugs targeting bacterial or plant AK but raises issues of selectivity in agricultural applications. There are no clinical drugs targeting AK in humans.

Other names

aspartokinaseβ-aspartokinaseaspartic kinaseAKATP:L-aspartate 4-phosphotransferase

Allosteric inhibition (by lysine and threonine); competitive inhibition (experimental); feedback inhibition