Molecular Modeling and Active Site Binding Mode Characterization of Aspartate β-Semialdehyde Dehydrogenase Family

Authors

  • Rajender Kumar,

    1. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S. A.S. Nagar, Punjab 160062, India tel.: +91-172-2292016; fax: +91-172-2214692
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  • Prabha Garg

    Corresponding author
    1. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S. A.S. Nagar, Punjab 160062, India tel.: +91-172-2292016; fax: +91-172-2214692
    2. Computer Centre, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India
    • Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S. A.S. Nagar, Punjab 160062, India tel.: +91-172-2292016; fax: +91-172-2214692
    Search for more papers by this author

Abstract

The enzyme aspartate β-semialdehyde dehydrogenase (ASADH) plays a vital role in biosynthesis of essential amino acids and several important metabolites in microbes and some higher plants. So this key enzyme can be targeted selectively in these microbes to exhibit anti-bacterial and fungicidal effects. In this work, molecular modeling and comparative active site binding mode studies were performed for understanding the mode of action, in silico insight into the 3D structure, enzyme-substrate interactions with natural substrate in this homologous enzyme family. During comparative sequence analysis, high diversity was found in the sequences of different ASADHs and exhibited the same key binding interactions with the substrate. Both, the functional carboxylic and the phosphate group of the substrate are engaged in a bidentate interaction with the guanidinium N atom of two key arginyl active site residues of ASADHs. These structural and active site binding mode characterization studies can further be used for designing the more potent and selective substrate analogues inhibitors against ASADH family.

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