ACT domains of the bifunctional enzyme aspartokinase (AK) - homoserine dehydrogenase (HSDH)
This CD includes the second of two ACT domains of the bifunctional enzyme aspartokinase (AK) - homoserine dehydrogenase (HSDH). The ACT domains are positioned between the N-terminal catalytic domain of AK and the C-terminal HSDH domain found in bacteria (Escherichia coli (EC) ThrA) and higher plants (Zea mays AK-HSDH). AK and HSDH are the first and third enzymes in the biosynthetic pathway of the aspartate family of amino acids. AK catalyzes the phosphorylation of Asp to P-aspartyl phosphate. HSDH catalyzes the NADPH-dependent conversion of Asp 3-semialdehyde to homoserine. HSDH is the first committed reaction in the branch of the pathway that leads to Thr and Met. In E. coli, ThrA is subject to allosteric regulation by the end product L-threonine and the native enzyme is reported to be tetrameric. As with bacteria, plant AK and HSDH are feedback inhibited by pathway end products. Maize AK-HSDH is a Thr-sensitive 180-kD enzyme. Arabidopsis AK-HSDH is an alanine-activated, threonine-sensitive enzyme whose ACT domains were shown to be involved in allosteric activation. Members of this CD belong to the superfamily of ACT regulatory domains.
Feature 1:putative threonine allosteric regulatory site
Evidence:
Comment:potentially involved in the binding of Thr.
Comment:Kinetic experiments on Arabidopsis AK-HSDH demonstrated that each regulatory (ACT) domain of the monomers of AK-HSDH contained two nonequivalent threonine binding sites, constituted in part by Gln443 and Gln524.
Comment:The interaction of threonine with Gln443 of Arabidopsis AK-HSDH led to inhibition of AK activity and facilitated the binding of a second threonine on Gln524. Interaction of this second threonine with Gln524 led to inhibition of HSDH activity.
Jiyao W et al.(2023). "The conserved domain database in 2023.",