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).   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.
Clinical significance [ edit ]
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 [ edit ]
6PGD is involved in cancer cell metabolism so 6PGD inhibitors have been sought.
See also [ edit ]
References [ edit ]
; 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.
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. doi: 10.1128/jb.172.7.4023-4031.1990. PMC . 213388 PMID 2113917.
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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. doi: 10.1002/j.1460-2075.1983.tb01535.x. PMC . 555222 PMID 6641716.
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.
6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1–AMPK signalling. 2015