Structural-functional analysis of drug target aspartate semialdehyde dehydrogenase.

Rajender Kumar, Prabha Garg, Rajkumar R, Vineet Diwakar, Nazam Khan, Gautam Kumar Meghwanshi

Journal: Drug discovery today 2024;29(3):103908

PMID: 38301800

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Abstract

Aspartate 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.

Address: Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, 106 91 Stockholm, Sweden.; Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar 160062, Punjab, India.; Clinical Laboratory Science Department, Applied Medical Science College, Shaqra University, Shaqra, Kingdom of Saudi Arabia.; Department of Microbiology, Maharaja Ganga Singh University, Bikaner 334004, India.; Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar 160062, Punjab, India. Electronic address: [email protected].

DOI: 10.1016/j.drudis.2024.103908

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MeSH Terms: Aspartate-Semialdehyde Dehydrogenase, Catalytic Domain, Enzyme Inhibitors