Phosphogluconate dehydrogenase

6PGD

File:PDB 1pgq EBI.jpg

Crystallographic structure of sheep 6-phosphogluconate dehydrogenase complexed with adenosine 2'-monophosphate.[1]

Identifiers
Symbol| 6PGD
Pfam| PF00393
Pfam clan| CL0106
InterPro| IPR006114
PROSITE| PDOC00390
SCOP| 2pgd
SUPERFAMILY| 2pgd
| Available protein structures:

Pfam| structures
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary
Phosphogluconate dehydrogenase

Identifiers
EC number| 1.1.1.44
CAS number| 9001-82-5
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
| Search

PMC| articles
PubMed| articles
NCBI| proteins
phosphogluconate dehydrogenase

Identifiers
Symbol| PGD
Entrez| 5226
HUGO| 8891
OMIM| 172200
RefSeq| NM_002631
UniProt| P52209
Other data
EC number| 1.1.1.44
Locus| Chr. 1 p36.3-36.13

6-Phosphogluconate dehydrogenase (6PGD) is an enzyme in the pentose phosphate pathway. It forms ribulose 5-phosphate from 6-phosphogluconate.

It is an oxidative carboxylase that catalyses the decarboxylating reduction 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 pathways (PPP).[2][3] Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequences are highly conserved.[4] The protein is a homodimer in which the monomers act independently:[3] each contains a large, mainly alpha-helical domain and a smaller beta-alpha-beta domain, containing a mixed parallel and anti-parallel 6-stranded beta sheet.[3] NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket.[3]

## Contents

* 1 Clinical significance
* 1.1 As a possible drug target
* 2 See also
* 3 References

## Clinical significance

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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

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6PGD is involved in cancer cell metabolism so 6PGD inhibitors have been sought.[5]

## See also

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* Parietin, a 6PGD inhibitor

## References

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1. ↑ PDB: 1PGQ​; Adams MJ, Ellis GH, Gover S, Naylor CE, Phillips C (July 1994). "Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism". Structure. 2 (7): 651–68. doi:10.1016/s0969-2126(00)00066-6. PMID 7922042.
2. ↑ Broedel SE, Wolf RE (July 1990). "Genetic tagging, cloning, and DNA sequence of the Synechococcus sp. strain PCC 7942 gene (gnd) encoding 6-phosphogluconate dehydrogenase". J. Bacteriol. 172 (7): 4023–31. PMC 213388. PMID 2113917.
3. ↑ 3.0 3.1 3.2 3.3 Adams MJ, Archibald IG, Bugg CE, Carne A, Gover S, Helliwell JR, Pickersgill RW, White SW (1983). "The three dimensional structure of sheep liver 6-phosphogluconate dehydrogenase at 2.6 A resolution". EMBO J. 2 (6): 1009–14. PMC 555222. PMID 6641716.
4. ↑ Reizer A, Deutscher J, Saier MH, Reizer J (May 1991). "Analysis of the gluconate (gnt) operon of Bacillus subtilis". Mol. Microbiol. 5 (5): 1081–9. doi:10.1111/j.1365-2958.1991.tb01880.x. PMID 1659648.
5. ↑ 6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1–AMPK signalling. 2015

This article incorporates text from the public domain Pfam and InterPro: IPR006114

Template:Pentose phosphate pathway

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Oxidoreductases: alcohol oxidoreductases (EC 1.1)

1.1.1: NAD/NADP acceptor|

* 3-hydroxyacyl-CoA dehydrogenase
* 3-hydroxybutyryl-CoA dehydrogenase
* Alcohol dehydrogenase
* Aldo-keto reductase
* 1A1
* 1B1
* 1B10
* 1C1
* 1C3
* 1C4
* 7A2
* Aldose reductase
* Beta-Ketoacyl ACP reductase
* Carbohydrate dehydrogenases
* Carnitine dehydrogenase
* D-malate dehydrogenase (decarboxylating)
* DXP reductoisomerase
* Glucose-6-phosphate dehydrogenase
* Glycerol-3-phosphate dehydrogenase
* HMG-CoA reductase
* IMP dehydrogenase
* Isocitrate dehydrogenase
* Lactate dehydrogenase
* L-threonine dehydrogenase
* L-xylulose reductase
* Malate dehydrogenase
* Malate dehydrogenase (decarboxylating)
* Malate dehydrogenase (NADP+)
* Malate dehydrogenase (oxaloacetate-decarboxylating)
* Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+)
* Phosphogluconate dehydrogenase
* Sorbitol dehydrogenase

* Hydroxysteroid dehydrogenase: 3β
* 3β-HSD
* NSDHL
* 11β
* 11β-HSD1
* 11β-HSD2
* 17β

1.1.2: cytochrome acceptor|

* D-lactate dehydrogenase (cytochrome)
* D-lactate dehydrogenase (cytochrome c-553)
* Mannitol dehydrogenase (cytochrome)

1.1.3: oxygen acceptor|

* Glucose oxidase
* L-gulonolactone oxidase
* Xanthine oxidase

1.1.4: disulfide as acceptor|

* Vitamin K epoxide reductase
* Vitamin-K-epoxide reductase (warfarin-insensitive)

1.1.5: quinone/similar acceptor|

* Malate dehydrogenase (quinone)
* Quinoprotein glucose dehydrogenase

1.1.99: other acceptors|

* Choline dehydrogenase
* L2HGDH

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Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Catalytically perfect enzyme
* Coenzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
* EC3 Hydrolases (list)
* EC4 Lyases (list)
* EC5 Isomerases (list)
* EC6 Ligases (list)

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