Saccharopine dehydrogenase

For other uses, see Saccharopine dehydrogenase (disambiguation).

Saccharopine Dehydrogenase
Saccharopine dehydrogenase from Magnaporthe grisea
Identifiers
Symbol	Saccharop_dh
Pfam	PF03435
Pfam clan	CL0063
InterPro	IPR005097
SCOP2	1ff9 / SCOPe / SUPFAM
Available protein structures: PDB   IPR005097 PF03435 (ECOD; PDBsum)   AlphaFold IPR005097 PF03435

saccharopine dehydrogenase (putative)
Identifiers
Symbol	SCCPDH
NCBI gene	51097
HGNC	24275
RefSeq	NM_016002
UniProt	Q8NBX0
Other data
Locus	Chr. 1 q44
Search for Structures Swiss-model Domains InterPro

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 1.5.1.7, EC 1.5.1.8, EC 1.5.1.9, and EC 1.5.1.10. It has an important function in lysine metabolism and catalyses a reaction in the α-aminoadipate 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.

Function

SDH uses nicotinamide adenine dinucleotide (NAD+) as an oxidant to catalyse the reversible oxidative deamination of the substrate, saccharopine. It forms the products, lysine and alpha-ketoglutaric acid. This is shown in the following chemical reaction: ^[1]

Saccharopine

+ NAD⁺

 

 

H₂O

H⁺

H₂O

H⁺

 

L-lysine

+ NADH +

 

α-Ketoglutaric acid

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. ^[2] In some organisms this enzyme is found as a bifunctional polypeptide with lysine ketoglutarate reductase (PF).

Homospermidine synthase proteins (EC). Homospermidine synthase (HSS) catalyses the synthesis of the polyamine homospermidine from 2 mol putrescine in an NAD⁺-dependent reaction. ^[3]

Structure

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). ^[4]

Clinical significance

Deficiencies are associated with hyperlysinemia. ^[5]

References

1. Kumar VP, West AH, Cook PF (June 2012). "Supporting role of lysine 13 and glutamate 16 in the acid-base mechanism of saccharopine dehydrogenase from Saccharomyces cerevisiae". Archives of Biochemistry and Biophysics. 522 (1): 57–61. doi:10.1016/j.abb.2012.03.027. PMID   22521736.
2. Vashishtha AK, West AH, Cook PF (June 2009). "Chemical mechanism of saccharopine reductase from Saccharomyces cerevisiae". Biochemistry. 48 (25): 5899–907. doi:10.1021/bi900599s. PMID   19449898.
3. Tholl D, Ober D, Martin W, Kellermann J, Hartmann T (September 1996). "Purification, molecular cloning and expression in Escherichia coli of homospermidine synthase from Rhodopseudomonas viridis". European Journal of Biochemistry. 240 (2): 373–9. doi: 10.1111/j.1432-1033.1996.0373h.x . PMID   8841401.
4. Andi B, Xu H, Cook PF, West AH (November 2007). "Crystal structures of ligand-bound saccharopine dehydrogenase from Saccharomyces cerevisiae". Biochemistry. 46 (44): 12512–21. doi:10.1021/bi701428m. PMID   17939687.
5. Sacksteder KA, Bier BJ, Morrell JC, Goodman BK, Geisbrecht BV, Cox RP, Gould SJ, Geraghty MT (June 2000). "Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia". American Journal of Human Genetics. 66 (6): 1736–1743. doi:10.1086/302919. PMC   1378037 . PMID   10775527.

• Saccharopine+Dehydrogenases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)