View source for 6-Phosphogluconate dehydrogenase

{{Short description|Class of enzymes}}
{{cs1 config|name-list-style=vanc}}
{{Infobox protein family
| Symbol = 6PGD
| Name = 6PGD
| image = PDB 1pgq EBI.jpg
| width = 
| caption = Crystallographic structure of sheep 6-phosphogluconate dehydrogenase complexed with adenosine 2'-monophosphate<ref name="pmid7922042">{{PDB|1PGQ}}; {{cite journal | vauthors = Adams MJ, Ellis GH, Gover S, Naylor CE, Phillips C | title = Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism | journal = Structure | volume = 2 | issue = 7 | pages = 651–68 |date=July 1994 | pmid = 7922042 | doi = 10.1016/s0969-2126(00)00066-6| doi-access =  }}</ref>
| Pfam = PF00393
| Pfam_clan = CL0106 
| InterPro = IPR006114
| SMART = 
| PROSITE = PDOC00390
| MEROPS = 
| SCOP = 2pgd
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
{{infobox enzyme
| Name       = Phosphogluconate dehydrogenase
| EC_number  = 1.1.1.44
| CAS_number = 9001-82-5
| GO_code    = 0008114
| image      = 1pgo.jpg
| width      = 270
| caption    = 6-phosphogluconate dehydrogenase dimer, Ovis aries
}}
{{protein
|Name=phosphogluconate dehydrogenase
|caption=
|image=
|width=
|HGNCid=8891
|Symbol=PGD
|AltSymbols=
|EntrezGene=5226
|OMIM=172200
|RefSeq=NM_002631
|UniProt=P52209
|PDB=
|ECnumber=1.1.1.44
|Chromosome=1
|Arm=p
|Band=36.3
|LocusSupplementaryData=-36.13
}}
'''6-Phosphogluconate dehydrogenase''' ('''6PGD''') is an [[enzyme]] in the [[pentose phosphate pathway]]. It forms [[ribulose 5-phosphate]] from [[6-phosphogluconate]]:

:6-phospho-D-gluconate + NAD(P)<sup>+</sup> <math>\rightleftharpoons</math> D-Ribulose 5-phosphate + CO2 + NAD(P)H + H<sup>+</sup>

It is an oxidative carboxylase that [[catalysis|catalyses]] the [[oxidative decarboxylation]] of [[6-phosphogluconate]] into [[ribulose 5-phosphate]] in the presence of [[NADP]]. This reaction is a component of the [[hexose]] mono-phosphate shunt and [[pentose phosphate pathway]]s (PPP).<ref name="pmid2113917">{{cite journal | vauthors = Broedel SE, Wolf RE | title = Genetic tagging, cloning, and DNA sequence of the Synechococcus sp. strain PCC 7942 gene (gnd) encoding 6-phosphogluconate dehydrogenase | journal = J. Bacteriol. | volume = 172 | issue = 7 | pages = 4023–31 |date=July 1990 | pmid = 2113917 | pmc = 213388 | doi = 10.1128/jb.172.7.4023-4031.1990}}</ref><ref name="pmid6641716">{{cite journal | vauthors = Adams MJ, Archibald IG, Bugg CE, Carne A, Gover S, [[John R. Helliwell|Helliwell JR]], Pickersgill RW, White SW | title = The three dimensional structure of sheep liver 6-phosphogluconate dehydrogenase at 2.6 A resolution | journal = EMBO J. | volume = 2 | issue = 6 | pages = 1009–14 | year = 1983 | pmid = 6641716 | pmc = 555222 | doi = 10.1002/j.1460-2075.1983.tb01535.x}}</ref> [[Prokaryotic]] and [[eukaryotic]] 6PGD are [[protein]]s of about 470 [[amino acid]]s whose [[sequence (biology)|sequence]]s are [[Conservation (genetics)|highly conserved]].<ref name="pmid1659648">{{cite journal | vauthors = Reizer A, Deutscher J, Saier MH, Reizer J | title = Analysis of the gluconate (gnt) operon of Bacillus subtilis | journal = Mol. Microbiol. | volume = 5 | issue = 5 | pages = 1081–9 |date=May 1991 | pmid = 1659648 | doi = 10.1111/j.1365-2958.1991.tb01880.x| s2cid = 2006623 }}</ref> The protein is a [[homodimer]] in which the [[monomer]]s act independently:<ref name="pmid6641716" /> each contains a large, mainly [[alpha helix|alpha-helical]] [[Domain (biology)|domain]] and a smaller beta-alpha-beta domain, containing a mixed parallel and anti-parallel 6-stranded [[beta sheet]].<ref name="pmid6641716" /> NADP is bound in a cleft in the small domain, the [[Enzyme substrate|substrate]] [[Binding (molecular)|binding]] in an adjacent pocket.<ref name="pmid6641716" />

== Biotechnological significance ==
Recently, 6PGD was demonstrated to catalyze also the reverse reaction (i.e. reductive [[carboxylation]]) ''in vivo''.<ref>{{cite journal | vauthors = Satanowski A, Dronsella B, Noor E, Vögeli B, He H, Wichmann P, Erb TJ, Lindner SN, Bar-Even A | display-authors = 6 | title = Awakening a latent carbon fixation cycle in Escherichia coli | journal = Nature Communications | volume = 11 | issue = 1 | pages = 5812 | date = November 2020 | pmid = 33199707 | pmc = 7669889 | doi = 10.1038/s41467-020-19564-5 | bibcode = 2020NatCo..11.5812S }}</ref> Experiments using ''Escherichia coli'' selection strains revealed that this reaction was efficient enough to support the formation of biomass based solely on [[Carbon dioxide|CO<sub>2</sub>]] and [[Pentose|pentose sugars]]. In the future, this property could be exploited for synthetic [[carbon fixation]] routes.

==Clinical significance==
Mutations within the gene coding this enzyme result in [[6-phosphogluconate dehydrogenase deficiency]], an [[autosomal]] hereditary disease affecting the red blood cells.

===As a possible drug target===
6PGD is involved in cancer cell metabolism so 6PGD inhibitors have been sought.<ref>[http://www.nature.com/ncb/journal/v17/n11/full/ncb3255.html 6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1–AMPK signalling. 2015]</ref>

==See also==
*[[Parietin]], a 6PGD inhibitor

==References==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Frampton EW, Wood WA | title = Carbohydrate oxidation by Pseudomonas fluorescens VI. Conversion of 2-keto-6-phosphogluconate to pyruvate | journal = The Journal of Biological Chemistry | volume = 236 | pages = 2571–7 | date = October 1961 | doi = 10.1016/S0021-9258(19)61700-X | pmid = 13894458 | doi-access = free }}
{{refend}}

{{InterPro content|IPR006114}}

{{Pentose phosphate pathway}}
{{Alcohol oxidoreductases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}

[[Category:NADPH-dependent enzymes]]
[[Category:NADH-dependent enzymes]]
[[Category:EC 1.1.1]]
[[Category:Pentose phosphate pathway]]