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Journal of Amino Acids
Volume 2011 (2011), Article ID 352538, 11 pages
http://dx.doi.org/10.4061/2011/352538
Review Article

The Catalytic Machinery of a Key Enzyme in Amino Acid Biosynthesis

1Department of Chemistry, University of Toledo, Toledo, OH 43606, USA
2Structural Biology Lab, Cold Spring Harbor Labs, Cold Spring Harbor, NY 11724, USA
3Rocky Mountain Labs, National Institutes of Health, Hamilton, MT 59840, USA
4Department of Pharmacology, Yale University, New Haven, CT 06520, USA

Received 2 October 2010; Accepted 7 November 2010

Academic Editor: Shandar Ahmad

Copyright © 2011 Ronald E. Viola et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aspartate pathway of amino acid biosynthesis is essential for all microbial life but is absent in mammals. Characterizing the enzyme-catalyzed reactions in this pathway can identify new protein targets for the development of antibiotics with unique modes of action. The enzyme aspartate β-semialdehyde dehydrogenase (ASADH) catalyzes an early branch point reaction in the aspartate pathway. Kinetic, mutagenic, and structural studies of ASADH from various microbial species have been used to elucidate mechanistic details and to identify essential amino acids involved in substrate binding, catalysis, and enzyme regulation. Important structural and functional differences have been found between ASADHs isolated from these bacterial and fungal organisms, opening the possibility for developing species-specific antimicrobial agents that target this family of enzymes.