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6-Phosphogluconate dehydrogenase

Class of enzymes

Summary

Class of enzymes

Field	Value
Symbol	6PGD
Name	6PGD
image	PDB 1pgq EBI.jpg
caption	Crystallographic structure of sheep 6-phosphogluconate dehydrogenase complexed with adenosine 2'-monophosphate
Pfam	PF00393
Pfam_clan	CL0106
InterPro	IPR006114
PROSITE	PDOC00390
SCOP	2pgd

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 oxidative decarboxylation of 6-phosphogluconic acid into ribulose 5-phosphate in the presence of oxidised NAD+. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP). Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequences are highly conserved. The protein is a homodimer in which the monomers act independently: 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. NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket.

Biotechnological significance

Recently, 6PGD was demonstrated to catalyze also the reverse reaction (i.e. reductive carboxylation) in vivo. Experiments using Escherichia coli selection strains revealed that this reaction was efficient enough to support the formation of biomass based solely on CO2 and 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.

References

(July 1994). "Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism". Structure.
{{KEGG enzyme. 1.1.1.44
(July 1990). "Genetic tagging, cloning, and DNA sequence of the Synechococcus sp. strain PCC 7942 gene (gnd) encoding 6-phosphogluconate dehydrogenase". J. Bacteriol..
(1983). "The three dimensional structure of sheep liver 6-phosphogluconate dehydrogenase at 2.6 A resolution". EMBO J..
(May 1991). "Analysis of the gluconate (gnt) operon of Bacillus subtilis". Mol. Microbiol..
(November 2020). "Awakening a latent carbon fixation cycle in Escherichia coli". Nature Communications.
[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]

Wikipedia Source

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nadph-dependent-enzymes nadh-dependent-enzymes ec-1.1.1 pentose-phosphate-pathway

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