F
IPR011534

Aspartate-semialdehyde dehydrogenase, gamma-type

InterPro entry
Short nameAsp_ADH_gamma-type
family relationships

Description

Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids -lysine, threonine, methionine and isoleucine -in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see
[1]
.

Aspartate-semialdehyde dehydrogenase (
1.2.1.11
), the second enzyme in the aspartate pathway, converts aspartyl phosphate to aspartate-semialdehyde, the branch point intermediate between the lysine and threonine/methionine pathways. Based on sequence alignments, the aspartate-semialdehyde dehydrogenase family appears to have at least three distinct subfamilies. Most studies have been performed on enzymes isolated from Gram-negative bacteria
[2, 3, 4, 5]
. The N-terminal domain forms the active site and NADP-binding pocket, while C-terminal domain is primarily involved in hydrophobic intersubunit contacts. The catalytic mechanism involves the formation of a covalent thioester acyl-enzyme intermediate mediated through nucleophilic attack by an active site cysteine residue on the substrate aspartyl phosphate. Release of inorganic phosphate is followed by hydride transfer from NADPH to yield the product. The recently described archaeal structure suggests that the two subgroups of aspartate semi-aldehyde dehydrogenase share similar structures and have an identical catalytic mechanism, despite their relatively low sequence identity
[6]
. Unlike the bacterial enzymes, the archaeal enzyme utilised both NAD and NADP as cofactor.

This entry represents a subfamily of aspartate semialdehyde dehydrogenases found mostly, though not exclusively, in proteobacteria.

References

1.The central enzymes of the aspartate family of amino acid biosynthesis. Viola RE. Acc. Chem. Res. 34, 339-49, (2001). View articlePMID: 11352712

2.Chemical and kinetic mechanisms of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. Karsten WE, Viola RE. Biochim. Biophys. Acta 1077, 209-19, (1991). View articlePMID: 1673060

3.Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase. Blanco J, Moore RA, Viola RE. Proc. Natl. Acad. Sci. U.S.A. 100, 12613-7, (2003). View articlePMID: 14559965

4.The role of substrate-binding groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase. Blanco J, Moore RA, Faehnle CR, Coe DM, Viola RE. Acta Crystallogr. D Biol. Crystallogr. 60, 1388-95, (2004). View articlePMID: 15272161

5.Critical catalytic functional groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase. Blanco J, Moore RA, Faehnle CR, Viola RE. Acta Crystallogr. D Biol. Crystallogr. 60, 1808-15, (2004). View articlePMID: 15388927

6.A new branch in the family: structure of aspartate-beta-semialdehyde dehydrogenase from Methanococcus jannaschii. Faehnle CR, Ohren JF, Viola RE. J. Mol. Biol. 353, 1055-68, (2005). View articlePMID: 16225889

GO terms

Cross References

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.