Aspartate-semialdehyde dehydrogenase (ASADH)

Aspartate-semialdehyde dehydrogenase (ASADH) is an essential oxidoreductase enzyme (EC 1.2.1.11) found in bacteria, fungi, and some plants, but absent in mammals. It catalyzes a key step in the aspartate pathway, converting β-aspartyl phosphate to L-aspartate-β-semialdehyde, a precursor for the biosynthesis of amino acids such as lysine, methionine, threonine, isoleucine, and leucine, as well as intermediates necessary for bacterial cell wall formation (e.g., diaminopimelate). ASADH is structurally well-characterized as a dimer or tetramer (depending on species), uses NADP+ as a cofactor, and contains a critical cysteine residue in its active site. Because its disruption is lethal to microorganisms, ASADH is a promising target for antibacterial, antifungal, and herbicidal drug development. Inhibitors under investigation typically act by blocking substrate or cofactor binding or through covalent modification of the active site. The enzyme is absent in humans, allowing for highly specific targeting of pathogens with minimal expected off-target toxicity[1][2][3][4][5][6][7][8][9].

Other names

Aspartate semialdehyde dehydrogenaseAspartic semialdehyde dehydrogenaseL-aspartate-beta-semialdehyde:NADP+ oxidoreductase (phosphorylating)Aspartic beta-semialdehyde dehydrogenaseASA dehydrogenase

Competitive inhibition of substrate or NADP+ binding to active site. Covalent inhibition at the essential cysteine in active site. Enzyme inactivation leads to interruption of amino acid biosynthesis, causing cell death or growth arrest in target organisms.