Phosphogluconate dehydrogenase

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6PGD
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
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 / EGO
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]

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.[5]

See also[edit]

References[edit]

  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 213388Freely accessible. PMID 2113917. 
  3. ^ 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. PMC 555222Freely accessible. 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