6-Phosphogluconate dehydrogenase

From WikiProjectMed
Jump to navigation Jump to search
6PGD
Crystallographic structure of sheep 6-phosphogluconate dehydrogenase complexed with adenosine 2'-monophosphate[1]
Identifiers
Symbol6PGD
PfamPF00393
Pfam clanCL0106
InterProIPR006114
PROSITEPDOC00390
SCOP22pgd / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Phosphogluconate dehydrogenase
6-phosphogluconate dehydrogenase dimer, Ovis aries
Identifiers
EC no.1.1.1.44
CAS no.9001-82-5
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
phosphogluconate dehydrogenase
Identifiers
SymbolPGD
NCBI gene5226
HGNC8891
OMIM172200
RefSeqNM_002631
UniProtP52209
Other data
EC number1.1.1.44
LocusChr. 1 p36.3-36.13
Search for
StructuresSwiss-model
DomainsInterPro

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)+ D-Ribulose 5-phosphate + CO2 + NAD(P)H + H+

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]

Biotechnological significance

Recently, 6PGD was demonstrated to catalyze also the reverse reaction (i.e. reductive carboxylation) in vivo.[5] 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.[6]

See also

References

  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. doi:10.1128/jb.172.7.4023-4031.1990. PMC 213388. 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. doi:10.1002/j.1460-2075.1983.tb01535.x. 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. S2CID 2006623.
  5. ^ Satanowski A, Dronsella B, Noor E, Vögeli B, He H, Wichmann P, et al. (November 2020). "Awakening a latent carbon fixation cycle in Escherichia coli". Nature Communications. 11 (1): 5812. Bibcode:2020NatCo..11.5812S. doi:10.1038/s41467-020-19564-5. PMC 7669889. PMID 33199707.
  6. ^ 6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1–AMPK signalling. 2015

Further reading

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