Saccharopine dehydrogenase from Magnaporthe grisea
|saccharopine dehydrogenase (putative)|
|Locus||Chr. 1 q44|
In molecular biology, the protein domain Saccharopine dehydrogenase (SDH), also named Saccharopine reductase, is an enzyme involved in the metabolism of the amino acid lysine, via an intermediate substance called saccharopine. The Saccharopine dehydrogenase enzyme can be classified under EC 22.214.171.124, EC 126.96.36.199, EC 188.8.131.52, and EC 184.108.40.206. It has an important function in lysine metabolism and catalyses a reaction in the alpha-Aminoadipic acid pathway. This pathway is unique to fungal organisms therefore, this molecule could be useful in the search for new antibiotics. This protein family also includes saccharopine dehydrogenase and homospermidine synthase. It is found in prokaryotes, eukaryotes and archaea.
Simplistically, SDH uses NAD+ as an oxidant to catalyse the reversible pyridine nucleotide dependent oxidative deamination of the substrate, Saccharopine, in order to form the products, lysine and alpha-ketoglutarate. This can be described by the following equation:
Saccharopine ⇌ lysine + alpha-ketoglutarate
Saccharopine dehydrogenase EC catalyses the condensation to of l-alpha-aminoadipate-delta-semialdehyde (AASA) with l-glutamate to give an imine, which is reduced by NADPH to give saccharopine. In some organisms this enzyme is found as a bifunctional polypeptide with lysine ketoglutarate reductase (PF).
There appears to be two protein domains of similar size. One domain is a Rossmann fold that binds NAD+/NADH, and the other is relatively similar. Both domains contain a six-stranded parallel beta-sheet surrounded by alpha-helices and loops (alpha/beta fold).
Deficiencies are associated with hyperlysinemia.
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