Aspartate-semialdehyde dehydrogenase

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aspartate-semialdehyde dehydrogenase
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Aspartate semialdehyde dehydrogenase tetramer, Trichophyton rubrum
Identifiers
EC no. 1.2.1.11
CAS no. 9000-98-0
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
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PMC articles
PubMed articles
NCBI proteins

In enzymology, an aspartate-semialdehyde dehydrogenase (EC 1.2.1.11) is an enzyme that is very important in the biosynthesis of amino acids in prokaryotes, fungi, and some higher plants. It forms an early branch point in the metabolic pathway forming lysine, methionine, leucine and isoleucine from aspartate. This pathway also produces diaminopimelate which plays an essential role in bacterial cell wall formation. There is particular interest in ASADH as disabling this enzyme proves fatal to the organism giving rise to the possibility of a new class of antibiotics, fungicides, and herbicides aimed at inhibiting it.[ citation needed ]

Contents

The enzyme catalyzes the reversible chemical reaction

L-aspartate 4-semialdehyde + phosphate + NADP+L-4-aspartyl phosphate + NADPH + H+

The 3 substrates of this enzyme are L-aspartate 4-semialdehyde, phosphate, and NADP+, whereas its 3 products are L-4-aspartyl phosphate, NADPH, and H+. However, under physiological conditions the reaction runs in the opposite direction.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of a donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is L-aspartate-4-semialdehyde:NADP+ oxidoreductase (phosphorylating). Other names in common use include aspartate semialdehyde dehydrogenase, aspartic semialdehyde dehydrogenase, L-aspartate-beta-semialdehyde:NADP+ oxidoreductase, (phosphorylating), aspartic beta-semialdehyde dehydrogenase, and ASA dehydrogenase. This enzyme participates in glycine, serine and threonine metabolism and lysine biosynthesis.

Aspartate-semialdehyde dehydrogenase may be cis-regulated by an Asd RNA motif found in the 5' UTR of some Asd genes.

Protein families

Semialdehyde dehydrogenase, dimerisation domain
Identifiers
SymbolSemialdhyde_dhC
Pfam PF02774
Pfam clan CL0139
InterPro IPR012280
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

This domain contains both N-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in arginine biosynthesis, and aspartate-semialdehyde dehydrogenase, [1] an enzyme involved in the biosynthesis of various amino acids from aspartate. It also contains the yeast and fungal Arg5,6 protein, which is cleaved into the enzymes N-acetyl-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in arginine biosynthesis. All proteins in this entry contain a dimerisation domain of semialdehyde dehydrogenase.

Structural studies

As of late 2007, 24 structures have been solved for this class of enzymes, with PDB accession codes 1BRM, 1GL3, 1MB4, 1MC4, 1NWC, 1NWH, 1NX6, 1OZA, 1PQP, 1PQU, 1PR3, 1PS8, 1PU2, 1Q2X, 1T4B, 1T4D, 1TA4, 1TB4, 1YS4, 2EP5, 2GYY, 2GZ1, 2GZ2, and 2GZ3.

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3
form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO form under biological conditions), and a side chain lysyl ((CH2)4NH2), classifying it as a basic, charged (at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the S configuration.

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<span class="mw-page-title-main">Saccharopine dehydrogenase (NADP+, L-glutamate-forming)</span>

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<small>L</small>-Aspartic-4-semialdehyde Chemical compound

L-Aspartic-4-semialdehyde is an α-amino acid derivative of aspartate. It is an important intermediate in the aspartate pathway, which is a metabolic pathway present in bacteria and plants. The aspartate pathway leads to the biosynthesis of a variety of amino acids from aspartate, including lysine, methionine, and threonine.

References

  1. Hadfield A, Kryger G, Ouyang J, Petsko GA, Ringe D, Viola R (1999). "Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis". J Mol Biol. 289 (4): 991–1002. doi:10.1006/jmbi.1999.2828. PMID   10369777.