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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)+
⇌
{\displaystyle \rightleftharpoons }
+ 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] homodimer in which the monomers act independently:[3] alpha-helical domain and a smaller beta-alpha-beta domain, containing a mixed parallel and anti-parallel 6-stranded beta sheet .[3] substrate binding in an adjacent pocket.[3]
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.[5]
See also References
^ 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 . ^ a b c d 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
Frampton EW, Wood WA (1961). "Carbohydrate oxidation by Pseudomonas fluorescens VI. Conversion of 2-keto-6-phosphogluconate to pyruvate". J. Biol. Chem . 236 : 2571–2577. PMID 13894458 .
Activity Regulation Classification Kinetics Types
