View source for Biology:Saccharopine dehydrogenase

{{other}}
{{Infobox protein family
| Symbol = Saccharop_dh
| Name = Saccharopine Dehydrogenase
| image = PDB 1e5l EBI.jpg
| width = 
| caption = Saccharopine dehydrogenase from ''Magnaporthe grisea''
| Pfam = PF03435
| Pfam_clan = CL0063 
| InterPro = IPR005097
| SMART = 
| PROSITE = 
| MEROPS = 
| SCOP = 1ff9
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
{{infobox protein
|Name=saccharopine dehydrogenase (putative)
|caption=
|image=
|width=
|HGNCid=24275
|Symbol=SCCPDH
|AltSymbols=
|EntrezGene=51097
|OMIM=
|RefSeq=NM_016002
|UniProt=Q8NBX0
|PDB=
|ECnumber=
|Chromosome=1
|Arm=q
|Band=44
|LocusSupplementaryData=
}}
In [[Biology:Molecular biology|molecular biology]], the [[Biology:Protein domain|protein domain]] '''Saccharopine dehydrogenase''' (SDH), also named Saccharopine reductase, is an [[Biology:Enzyme|enzyme]] involved in the [[Biology:Metabolism|metabolism]] of the [[Chemistry:Amino acid|amino acid]] [[Chemistry:Lysine|lysine]], via an intermediate substance called [[Chemistry:Saccharopine|saccharopine]]. The Saccharopine dehydrogenase enzyme can be classified under {{EC number|1.5.1.7}}, {{EC number|1.5.1.8}}, {{EC number|1.5.1.9}}, and {{EC number|1.5.1.10}}. It has an important function in lysine metabolism and catalyses a reaction in the alpha-Aminoadipic acid pathway. This pathway is unique to [[Biology:Fungi|fungal]] organisms therefore, this molecule could be useful in the search for new antibiotics. This protein family also includes saccharopine [[Biology:Dehydrogenase|dehydrogenase]] and homospermidine [[Biology:Synthase|synthase]]. It is found in prokaryotes, eukaryotes and [[Biology:Archaea|archaea]].

== Function ==
Simplistically, SDH uses [[Chemistry:Nicotinamide adenine dinucleotide|NAD+]] as an [[Chemistry:Redox|oxidant]] to catalyse the reversible [[Chemistry:Pyridine|pyridine]] [[Biology:Nucleotide|nucleotide]] dependent oxidative [[Biology:Deamination|deamination]] of the [[Biology:Substrate (biochemistry)|substrate]], Saccharopine, in order to form the products, lysine and alpha-ketoglutarate.
This can be described by the following equation:<ref name="pmid22521736">{{cite journal | vauthors = Kumar VP, West AH, Cook PF | title = Supporting role of lysine 13 and glutamate 16 in the acid-base mechanism of saccharopine dehydrogenase from Saccharomyces cerevisiae | journal = Archives of Biochemistry and Biophysics | volume = 522 | issue = 1 | pages = 57–61 | date = June 2012 | pmid = 22521736 | doi = 10.1016/j.abb.2012.03.027 }}</ref>

::::SDH
Saccharopine    ⇌   lysine + alpha-ketoglutarate

Saccharopine dehydrogenase [http://expasy.org/enzyme/1.5.1.10 EC] [[Chemistry:Catalysis|catalyses]] the condensation to of l-alpha-aminoadipate-delta-semialdehyde (AASA) with l-glutamate to give an imine, which is [[Chemistry:Redox|reduced]] by NADPH to give saccharopine.<ref name="pmid19449898">{{cite journal | vauthors = Vashishtha AK, West AH, Cook PF | title = Chemical mechanism of saccharopine reductase from Saccharomyces cerevisiae | journal = Biochemistry | volume = 48 | issue = 25 | pages = 5899–907 | date = June 2009 | pmid = 19449898 | doi = 10.1021/bi900599s }}</ref> In some organisms this [[Biology:Enzyme|enzyme]] is found as a bifunctional polypeptide with [[Chemistry:Lysine|lysine]] ketoglutarate reductase (PF).

Homospermidine [[Biology:Thromboxane-A synthase|synthase]] [[Biology:Protein|protein]]s ([http://expasy.org/enzyme/2.5.1.44 EC]). Homospermidine synthase (HSS) [[Biology:Biocatalysis|catalyses]] the synthesis of the [[Biology:Polyamine|polyamine]] homospermidine from 2 [[Mole (unit)|mol]] [[Chemistry:Putrescine|putrescine]] in an NAD<sup>+</sup>-dependent reaction.<ref name="pmid8841401">{{cite journal | vauthors = Tholl D, Ober D, Martin W, Kellermann J, Hartmann T | title = Purification, molecular cloning and expression in Escherichia coli of homospermidine synthase from Rhodopseudomonas viridis | journal = European Journal of Biochemistry | volume = 240 | issue = 2 | pages = 373–9 | date = September 1996 | pmid = 8841401 | doi = 10.1111/j.1432-1033.1996.0373h.x | doi-access = free }}</ref>

== Structure ==
There appears to be two  protein domains of similar size. One domain is a [[Biology:Rossmann fold|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).<ref name="pmid17939687">{{cite journal | vauthors = Andi B, Xu H, Cook PF, West AH | title = Crystal structures of ligand-bound saccharopine dehydrogenase from Saccharomyces cerevisiae | journal = Biochemistry | volume = 46 | issue = 44 | pages = 12512–21 | date = November 2007 | pmid = 17939687 | doi = 10.1021/bi701428m }}</ref>

==Clinical significance==
Deficiencies are associated with [[Medicine:Hyperlysinemia|hyperlysinemia]].

== References ==
{{Reflist}}
* {{MeshName|Saccharopine+Dehydrogenases}}

{{CH-NH oxidoreductases}}
{{Amino acid metabolism enzymes}}

[[Category:Protein domains]]
[[Category:Protein families]]

{{Sourceattribution|Saccharopine dehydrogenase}}