InterPro domain: IPR006183

This entry represents prokaryotic and eukaryotic 6PGD and a truncated prokaryotic 6PGD that lacks of a central region of about 140 residues, such as yqeC from Bacillus subtilis [ 1 ]. Bacillus subtilis contains three classes of 6-phosphogluconate dehydrogenases (6PGD), including Gnd (YqjI), GntZ and YqeC. All of them are included in this entry. YgjiI is NADP+ dependent, while GntZ and YqeC are NAD+-dependent [ 2 ].

6-Phosphogluconate dehydrogenase ( 1.1.1.44 ) (6PGD) is a key enzyme that produces NADPH by converting 6-phospho D-gluconolactone to D-ribulose 5-phosphate in the pentose phosphate pathways (PPP) [ 2 , 3 ]. NADPH provides the major reducing power required for lipid production and protecting the cell against oxidative stress. 6PGD has been extensively studied with respect to kinetics, regulation, role in pentose-shunt production of NADPH and lipogenesis, and population genetics [ 4 ]. 6PGD is associated with several human disorders including cancer and Alzheimer's disease. The structure of the budding yeast 6PGD (also known as Gnd1) has been revealed [ 5 ].

Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequence are highly conserved [ 6 ]. The protein is a homodimer in which the monomers act independently [ 7 ]: 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 [ 7 , 7 ]. NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket [ 7 ].

1. The Bacillus subtilis yqjI gene encodes the NADP+-dependent 6-P-gluconate dehydrogenase in the pentose phosphate pathway. J. Bacteriol. 186, 4528-34
2. Genetic tagging, cloning, and DNA sequence of the Synechococcus sp. strain PCC 7942 gene (gnd) encoding 6-phosphogluconate dehydrogenase. J. Bacteriol. 172, 4023-31
3. The three dimensional structure of sheep liver 6-phosphogluconate dehydrogenase at 2.6 A resolution. EMBO J. 2, 1009-14
4. Purification and characterization of 6-phosphogluconate dehydrogenase from the wing-polymorphic cricket, Gryllus firmus, and assessment of causes of morph-differences in enzyme activity. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 172-173, 29-38
5. Crystal structure of Saccharomyces cerevisiae 6-phosphogluconate dehydrogenase Gnd1. BMC Struct. Biol. 7, 38
6. Analysis of the gluconate (gnt) operon of Bacillus subtilis. Mol. Microbiol. 5, 1081-9