Structural-functional analysis of drug target aspartate semialdehyde dehydrogenase

Drug Discov Today. 2024 Jan 30;29(3):103908. doi: 10.1016/j.drudis.2024.103908. Online ahead of print.ABSTRACTAspartate β-semialdehyde dehydrogenase (ASADH) is a key enzyme in the biosynthesis of essential amino acids in microorganisms and some plants. Inhibition of ASADHs can be a potential drug target for developing novel antimicrobial and herbicidal compounds. This review covers up-to-date information about sequence diversity, ligand/inhibitor-bound 3D structures, potential inhibitors, and key pharmacophoric features of ASADH useful in designing novel and target-specific inhibitors of ASADH. Most reported ASADH inhibitors have two highly electronegative functional groups that interact with two key arginyl residues present in the active site of ASADHs. The structural information, active site binding modes, and key interactions between the enzyme and inhibitors serve as the basis for designing new and potent inhibitors against the ASADH family.PMID:38301800 | DOI:10.1016/j.drudis.2024.103908
Source: Drug Discovery Today - Category: Drugs & Pharmacology Authors: Source Type: research