6-phosphogluconate dehydrogenase

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{{STRUCTURE_1pgj| PDB=1pgj | SIZE=400| SCENE= |right|CAPTION=6-phosphogluconate dehydrogenase dimer complex with sulfate, [[1pgj]]}}
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<StructureSection load='1pgo' size='400' side='right' caption='Sheep 6-phosphogluconate dehydrogenase complex with cofactor NADP and sulfate (PDB code [[1pgo]])' scene='49/491981/Cv/2'>
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==Introduction==
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Please use the "3D" button above this box to insert a Jmol applet (molecule) on this page.
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'''6-phosphogluconate dehydrogenase''' or '''imine reductase''' (it's NAD-binding domain) (6PGD) is an enzyme that plays a key role in the pentose phosphate pathway (PPP), also known as the phosphogluconate pathway. The PPP is a metabolic pathway that operates alongside glycolysis and is involved in the production of NADPH (nicotinamide adenine dinucleotide phosphate) and ribose-5-phosphate, which are essential for various cellular processes.
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6PGD catalyzes the oxidative decarboxylation of 6-phosphogluconate to produce ribulose-5-phosphate and NADPH. The reaction also releases carbon dioxide (CO2). This step in the pathway is critical for generating NADPH, which serves as a reducing agent for various biosynthetic reactions, including fatty acid and cholesterol synthesis, as well as maintaining cellular redox balance.
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The activity of 6PGD is regulated by various factors, including the availability of substrates, allosteric effectors, and post-translational modifications. The enzyme is found in most tissues and is particularly abundant in tissues with high rates of biosynthesis or redox demands, such as the liver, adipose tissue, and red blood cells.
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Deficiencies or dysregulation of 6PGD can have significant implications for cellular metabolism and redox homeostasis. Mutations in the gene encoding 6PGD have been associated with an inherited metabolic disorder called 6-phosphogluconate dehydrogenase deficiency, which can lead to hemolytic anemia due to reduced NADPH production and increased oxidative stress in red blood cells.
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Overall, 6-phosphogluconate dehydrogenase (6PGD) is an enzyme involved in the pentose phosphate pathway. It catalyzes the oxidative decarboxylation of 6-phosphogluconate, producing ribulose-5-phosphate and NADPH. This enzyme is important for providing NADPH for biosynthetic processes and maintaining cellular redox balance.
== Function ==
== Function ==
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'''6-phosphogluconate dehydrogenase''' (6PGD) catalyzes the decarboxylation reduction of 6-phosphogluconate (6PG) to ribulose 5-phosphate and CO2. This reaction is part of the pentose phosphate pathway. NADP is a cofactor in this reaction and is converted to NADPH.
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'''6PGD''' specifically catalyzes the decarboxylation reduction of 6-phosphogluconate (6PG) to ribulose 5-phosphate and CO2. This reaction is part of the pentose phosphate pathway. NADP is a cofactor in this reaction and is converted to NADPH.<ref>PMID:7922402</ref>
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*<scene name='49/491981/Cv/4'>NADP interactions</scene> with Sheep 6-phosphogluconate dehydrogenase (PDB code [[1pgo]]). Water molecules are shown as red spheres.
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*<scene name='49/491981/Cv/5'>NADP binding cavity</scene>.
== Disease ==
== Disease ==
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6PGD deficiency is an autosomal hereditary disease which manifests itself by abnormal breakdown of red blood cells. Treatment involves avoidance of drugs or foods which can cause hemolysis.
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6PGD deficiency is an autosomal hereditary disease which manifests itself by abnormal breakdown of red blood cells. Treatment involves avoidance of drugs or foods which can cause hemolysis.<ref>PMID:18159462</ref>
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== Relevance ==
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== Structural highlights ==
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==3D structures of 6-phosphogluconate dehydrogenase==
==3D structures of 6-phosphogluconate dehydrogenase==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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[[6-phosphogluconate dehydrogenase 3D structures]]
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*6PGD
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**[[2pgd]] - s6PGD – sheep<BR />
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**[[1pgj]] - 6PGD – ''Trypanosoma brucei''<BR />
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**[[2p4q]] - 6PGD – yeast<BR />
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**[[2zyg]] - 6PGD (mutant) – ''Klebsiella pneumonia''<BR />
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**[[4e21]] - Gm6PGD – ''Geobacter metallireducens''
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**[[4gbj]] – Df6PGD – ''Dyadobacter fermentans''<br />
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**[[4gwg]] - h6PGD – human<br />
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*6PGD binary complex
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**[[1pgn]] – s6PGD + Br-NADP<BR />
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**[[1pgo]] - s6PGD + NADP<BR />
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**[[1pgp]] - s6PGD + 6PG<BR />
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**[[1pgq]] - s6PGD + AMP<BR />
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**[[2jkv]] - h6PGD + NADP <BR />
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**[[4gwk]] - h6PGD + 3PG<br />
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**[[2zya]] - Ec6PGD (mutant) + 6PG – ''Escherichia coli''<BR />
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**[[2w8z]], [[2w90]] - 6PGD + 6PG – ''Geobacillus stearothermophilus''<BR />
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**[[2iyo]] - Ll6PGD + 6PG – ''Lactococcus lactis''<BR />
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**[[2zyd]] - Ec6PGD (mutant) + glucose
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*6PGD ternary complex
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**[[2iz1]] - Ll6PGD + inhibitor + ADP <BR />
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</StructureSection>
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**[[3fwn]] - Ec6PGD (mutant) + ADP + 6PG<br />
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**[[3pef]] – Gm6PGD (mutant) + NADP + monophosphoadenosine diphosphoribose<br />
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**[[3w6u]] – Pc6PGD + NADP + monophosphoadenosine diphosphoribose – ''Pyrobaculum calidifontis''<br />
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**[[3w6z]] – Pc6PGD (mutant) + NADP + monophosphoadenosine diphosphoribose <br />
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*6PGD quaternary complex
 
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**[[2iyp]] - Ll6PGD + ADP + ribulose 5-phosphate + NADP<BR />
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== References ==
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**[[2iz0]] - Ll6PGD + inhibitor + ADP + NADP<BR />
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<references/>
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}}
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[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Sheep 6-phosphogluconate dehydrogenase complex with cofactor NADP and sulfate (PDB code 1pgo)

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References

  1. ↑ Beam TR Jr. Quinolone therapy in intensive care unit settings. New Horiz. 1993 May;1(2):187-93. PMID:7922402
  2. ↑ Monga A, Makkar RP, Arora A, Mukhopadhyay S, Gupta AK. Case report: Acute hepatitis E infection with coexistent glucose-6-phosphate dehydrogenase deficiency. Can J Infect Dis. 2003 Jul;14(4):230-1. PMID:18159462

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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