6-Phosphogluconate dehydrogenase

{{Infobox protein family

| Symbol = 6PGD

| Name = 6PGD

| image = PDB 1pgq EBI.jpg

| width =

| caption = Crystallographic structure of sheep 6-phosphogluconate dehydrogenase complexed with adenosine 2'-monophosphate{{PDB|1PGQ}}; {{cite journal | vauthors = Adams MJ, Ellis GH, Gover S, Naylor CE, Phillips C | title = Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism | journal = Structure | volume = 2 | issue = 7 | pages = 651–68 |date=July 1994 | pmid = 7922042 | doi = 10.1016/s0969-2126(00)00066-6| doi-access = }}

| Pfam = PF00393

| Pfam_clan = CL0106

| InterPro = IPR006114

| SMART =

| PROSITE = PDOC00390

| MEROPS =

| SCOP = 2pgd

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

{{infobox enzyme

| Name = Phosphogluconate dehydrogenase

| EC_number = 1.1.1.44

| CAS_number = 9001-82-5

| GO_code = 0008114

| image = 1pgo.jpg

| width = 270

| caption = 6-phosphogluconate dehydrogenase dimer, Ovis aries

}}

{{protein

|Name=phosphogluconate dehydrogenase

|caption=

|image=

|width=

|HGNCid=8891

|Symbol=PGD

|AltSymbols=

|EntrezGene=5226

|OMIM=172200

|RefSeq=NM_002631

|UniProt=P52209

|PDB=

|ECnumber=1.1.1.44

|Chromosome=1

|Arm=p

|Band=36.3

|LocusSupplementaryData=-36.13

}}

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

It is an oxidative carboxylase that catalyses the oxidative decarboxylation 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).{{cite journal | vauthors = Broedel SE, Wolf RE | title = Genetic tagging, cloning, and DNA sequence of the Synechococcus sp. strain PCC 7942 gene (gnd) encoding 6-phosphogluconate dehydrogenase | journal = J. Bacteriol. | volume = 172 | issue = 7 | pages = 4023–31 |date=July 1990 | pmid = 2113917 | pmc = 213388 | doi = 10.1128/jb.172.7.4023-4031.1990}}{{cite journal | vauthors = Adams MJ, Archibald IG, Bugg CE, Carne A, Gover S, Helliwell JR, Pickersgill RW, White SW | title = The three dimensional structure of sheep liver 6-phosphogluconate dehydrogenase at 2.6 A resolution | journal = EMBO J. | volume = 2 | issue = 6 | pages = 1009–14 | year = 1983 | pmid = 6641716 | pmc = 555222 | doi = 10.1002/j.1460-2075.1983.tb01535.x}} Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequences are highly conserved.{{cite journal | vauthors = Reizer A, Deutscher J, Saier MH, Reizer J | title = Analysis of the gluconate (gnt) operon of Bacillus subtilis | journal = Mol. Microbiol. | volume = 5 | issue = 5 | pages = 1081–9 |date=May 1991 | pmid = 1659648 | doi = 10.1111/j.1365-2958.1991.tb01880.x| s2cid = 2006623 }} 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.{{cite journal | vauthors = Satanowski A, Dronsella B, Noor E, Vögeli B, He H, Wichmann P, Erb TJ, Lindner SN, Bar-Even A | display-authors = 6 | title = Awakening a latent carbon fixation cycle in Escherichia coli | journal = Nature Communications | volume = 11 | issue = 1 | pages = 5812 | date = November 2020 | pmid = 33199707 | pmc = 7669889 | doi = 10.1038/s41467-020-19564-5 | bibcode = 2020NatCo..11.5812S }} 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.[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]

6-Phosphogluconate dehydrogenase

Biotechnological significance

Clinical significance

=As a possible drug target=

See also

References

Further reading