InterPro domain: IPR041743

This entry includes the N-terminal catalytic domain of aspartokinase (AK) of the bifunctional enzyme AK-homoserine dehydrogenase (HSDH). These aspartokinases are found in bacteria (E. coli AKI-HSDHI, ThrA and E. coli AKII-HSDHII, MetL) and higher plants (Z. 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. ThrA and MetL are involved in threonine and methionine biosynthesis, respectively. 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 180kDa enzyme. Arabidopsis AK-HSDH is an alanine-activated, threonine-sensitive enzyme whose ACT domains, located C-terminal to the AK catalytic domain, were shown to be involved in allosteric activation [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].

1. Nucleotide sequence of the thrA gene of Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 77, 5730-3
2. Nucleotide sequence of the metL gene of Escherichia coli. Its product, the bifunctional aspartokinase ii-homoserine dehydrogenase II, and the bifunctional product of the thrA gene, aspartokinase I-homoserine dehydrogenase I, derive from a common ancestor. J. Biol. Chem. 258, 3028-31
3. Production and characterization of bifunctional enzymes. Domain swapping to produce new bifunctional enzymes in the aspartate pathway. Biochemistry 41, 3720-5
4. The aspartic acid metabolic pathway, an exciting and essential pathway in plants. Amino Acids 30, 143-62
5. Molecular genetics of the maize (Zea mays L.) aspartate kinase-homoserine dehydrogenase gene family. Plant Physiol. 106, 1303-12
6. Identification of six novel allosteric effectors of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase isoforms. Physiological context sets the specificity. J. Biol. Chem. 280, 41178-83
7. Mechanism of control of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase by threonine. J. Biol. Chem. 278, 5361-6
8. Nucleotide sequence of the Serratia marcescens threonine operon and analysis of the threonine operon mutations which alter feedback inhibition of both aspartokinase I and homoserine dehydrogenase I. J. Bacteriol. 175, 785-94