Summary: Glucose-6-phosphate dehydrogenase, NAD binding domain
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Glucose-6-phosphate dehydrogenase Edit Wikipedia article
| Glucose-6-phosphate dehydrogenase | |||||||||
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| Identifiers | |||||||||
| EC number | 1.1.1.49 | ||||||||
| CAS number | 9001-40-5 | ||||||||
| 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 | ||||||||
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| Glucose-6-phosphate dehydrogenase, NAD binding domain | |||||||||
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| glucose 6-phosphate dehydrogenase from leuconostoc mesenteroides | |||||||||
| Identifiers | |||||||||
| Symbol | G6PD_N | ||||||||
| Pfam | PF00479 | ||||||||
| Pfam clan | CL0063 | ||||||||
| InterPro | IPR022674 | ||||||||
| PROSITE | PDOC00067 | ||||||||
| SCOP | 1dpg | ||||||||
| SUPERFAMILY | 1dpg | ||||||||
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| Glucose-6-phosphate dehydrogenase, C-terminal domain | |||||||||
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| Identifiers | |||||||||
| Symbol | G6PD_C | ||||||||
| Pfam | PF02781 | ||||||||
| PROSITE | PDOC00067 | ||||||||
| SCOP | 1dpg | ||||||||
| SUPERFAMILY | 1dpg | ||||||||
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Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) is a cytosolic enzyme in the pentose phosphate pathway (see image), a metabolic pathway that supplies reducing energy to cells (such as erythrocytes) by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH in turn maintains the level of glutathione in these cells that helps protect the red blood cells against oxidative damage. Of greater quantitative importance is the production of NADPH for tissues actively engaged in biosynthesis of fatty acids and/or isoprenoids, such as the liver, mammary glands, adipose tissue, and the adrenal glands. G6PD reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH while oxidizing glucose-6-phosphate.[1]
It is notable in humans when there is a genetic deficiency of G6PD which predisposes to non-immune hemolytic anemia .
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[edit] Species distribution
G6PD is widely distributed in many species from bacteria to humans. In higher plants, several isoforms of G6PDH have been reported, which are localized in the cytosol, the plastidic stroma, and peroxisomes.[2]
[edit] Regulation
Glucose-6-phosphate dehydrogenase is stimulated by its substrate Glucose 6 Phosphate. The usual ratio of NADPH/NADP+ in the cytosol of tissues engaged in biosyntheses is about 100/1. Increased utilization of NADPH for fatty acid biosynthesis will dramatically increase the level of NADP+, thus stimulating G6PD to produce more NADPH.
G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of the pentose phosphate pathway.
G6PD is one of a number of glycolytic enzymes activated by the transcription factor Hypoxia-inducible factor 1 (HIF1).[3]
[edit] Clinical significance
G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. Two transcript variants encoding different isoforms have been found for this gene.[4]
Glucose-6-phosphate dehydrogenase deficiency is very common worldwide, and causes acute hemolytic anemia in the presence of simple infection, ingestion of fava beans, or reaction with certain medicines, antibiotics, antipyretics, and antimalarials.[5]
Cell growth and proliferation are affected by G6PD.[6] G6PD inhibitors are under investigation to treat cancers and other conditions.[3] DHEA is a G6PD inhibitor.[6]
[edit] See also
[edit] References
- ^ Aster J, Kumar V, Robbins SL, Abbas AK, Fausto N, Cotran RS (2010). Robbins and Cotran pathologic basis of disease. Saunders/Elsevier. pp. Kindle Locations 33340â33341. ISBN 1-4160-3121-9.
- ^ Corpas FJ, Barroso JB, Sandalio LM, Distefano S, Palma JM, Lupiáñez JA, Del RÃo LA (March 1998). "A dehydrogenase-mediated recycling system of NADPH in plant peroxisomes". Biochem. J. 330 ( Pt 2) (Pt 2): 777â84. PMC 1219205. PMID 9480890.
- ^ a b de Lartigue J (2012-06-12). "Cancer Research Moves Beyond the Original Hallmarks of Cancer". OncLive.
- ^ "Entrez Gene: G6PD glucose-6-phosphate dehydrogenase".
- ^ Cappellini MD, Fiorelli G (January 2008). "Glucose-6-phosphate dehydrogenase deficiency". Lancet 371 (9606): 64â74. doi:10.1016/S0140-6736(08)60073-2. PMID 18177777.
- ^ a b Tian WN, Braunstein LD, Pang J, Stuhlmeier KM, Xi QC, Tian X, Stanton RC (April 1998). "Importance of glucose-6-phosphate dehydrogenase activity for cell growth". J. Biol. Chem. 273 (17): 10609â17. doi:10.1074/jbc.273.17.10609. PMID 9553122.
[edit] Further reading
- Vulliamy T, Beutler E, Luzzatto L (1993). "Variants of glucose-6-phosphate dehydrogenase are due to missense mutations spread throughout the coding region of the gene". Hum. Mutat. 2 (3): 159â67. doi:10.1002/humu.1380020302. PMID 8364584.
- Mason PJ (1996). "New insights into G6PD deficiency". Br. J. Haematol. 94 (4): 585â91. PMID 8826878.
- Wajcman H, Galactéros F (2004). "[Glucose 6-phosphate dehydrogenase deficiency: a protection against malaria and a risk for hemolytic accidents]". C. R. Biol. 327 (8): 711â20. doi:10.1016/j.crvi.2004.07.010. PMID 15506519.
[edit] External links
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Glucose-6-phosphate dehydrogenase, NAD binding domain Provide feedback
No Pfam abstract.
Literature references
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Cosgrove MS, Naylor C, Paludan S, Adams MJ, Levy HR; , Biochemistry. 1998;37:2759-2767.: On the mechanism of the reaction catalyzed by glucose 6-phosphate dehydrogenase. PUBMED:9485426 EPMC:9485426
External database links
| HOMSTRAD: | G6PD_NC G6PD |
| PANDIT: | PF00479 |
| PRINTS: | PR00079 |
| PROSITE: | PDOC00067 |
| Pseudofam: | PF00479 |
| SCOP: | 1dpg |
| SYSTERS: | G6PD_N |
This tab holds annotation information from the InterPro database.
InterPro entry IPR022674
Glucose-6-phosphate dehydrogenase (EC) (G6PDH) is a ubiquitous protein, present in bacteria and all eukaryotic cell types [PUBMED:2838391]. The enzyme catalyses the the first step in the pentose pathway, i.e. the conversion of glucose-6-phosphate to gluconolactone 6-phosphate in the presence of NADP, producing NADPH. The ubiquitous expression of the enzyme gives it a major role in the production of NADPH for the many NADPH-mediated reductive processes in all cells [PUBMED:3393536]. Deficiency of G6PDH is a common genetic abnormality affecting millions of people worldwide. Many sequence variants, most caused by single point mutations, are known, exhibiting a wide variety of phenotypes [PUBMED:3393536].
This entry represents the NAD-binding domain of glucose-6-phosphate dehydrogenase.Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | NADP binding (GO:0050661) |
| glucose-6-phosphate dehydrogenase activity (GO:0004345) | |
| Biological process | glucose metabolic process (GO:0006006) |
| oxidation-reduction process (GO:0055114) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan NADP_Rossmann (CL0063), which contains the following 180 members:
2-Hacid_dh_C 3Beta_HSD 3HCDH_N adh_short adh_short_C2 ADH_zinc_N ADH_zinc_N_2 AdoHcyase_NAD AdoMet_MTase AlaDh_PNT_C Amino_oxidase ApbA AviRa Bac_GDH Bin3 CheR CMAS CmcI CoA_binding CoA_binding_2 CoA_binding_3 Cons_hypoth95 DAO DapB_N DFP DNA_circ_N DNA_methylase DOT1 DREV dTMP_synthase DUF1442 DUF1776 DUF2431 DUF268 DUF3321 DUF43 DUF633 DUF938 DXP_redisom_C DXP_reductoisom Eco57I ELFV_dehydrog Eno-Rase_FAD_bd Eno-Rase_NADH_b Enoyl_reductase Epimerase F420_oxidored FAD_binding_2 FAD_binding_3 FAD_oxidored Fibrillarin FMO-like FmrO FtsJ G-7-MTase G6PD_N GCD14 GDI GFO_IDH_MocA GIDA GidB GLF Glyco_hydro_4 GMC_oxred_N Gp_dh_N GRAS GRDA HI0933_like HIM1 IlvN K_oxygenase KR LCM Ldh_1_N Lycopene_cycl Malic_M Mannitol_dh Met_10 Methyltrans_Mon Methyltrans_SAM Methyltransf_10 Methyltransf_11 Methyltransf_12 Methyltransf_15 Methyltransf_16 Methyltransf_17 Methyltransf_18 Methyltransf_19 Methyltransf_2 Methyltransf_20 Methyltransf_21 Methyltransf_22 Methyltransf_23 Methyltransf_24 Methyltransf_25 Methyltransf_26 Methyltransf_27 Methyltransf_28 Methyltransf_29 Methyltransf_3 Methyltransf_30 Methyltransf_31 Methyltransf_32 Methyltransf_4 Methyltransf_5 Methyltransf_7 Methyltransf_8 Methyltransf_9 Methyltransf_PK MethyltransfD12 MetW Mg-por_mtran_C Mqo MT-A70 MTS Mur_ligase N2227 N6-adenineMlase N6_Mtase N6_N4_Mtase NAD_binding_10 NAD_binding_11 NAD_binding_2 NAD_binding_3 NAD_binding_4 NAD_binding_5 NAD_binding_7 NAD_binding_8 NAD_binding_9 NAD_Gly3P_dh_N NAS NmrA NNMT_PNMT_TEMT NodS Nol1_Nop2_Fmu Nol1_Nop2_Fmu_2 NSP13 OCD_Mu_crystall PARP_regulatory PCMT PDH Polysacc_synt_2 Pox_MCEL Prenylcys_lyase PrmA PRMT5 Pyr_redox Pyr_redox_2 Pyr_redox_3 RmlD_sub_bind Rossmann-like rRNA_methylase RrnaAD Rsm22 RsmJ Saccharop_dh SAM_MT SE Semialdhyde_dh Shikimate_DH Spermine_synth Strep_67kDa_ant TehB THF_DHG_CYH_C Thi4 ThiF TPMT TrkA_N TRM TRM13 tRNA_U5-meth_tr Trp_halogenase TylF Ubie_methyltran UDPG_MGDP_dh_N UPF0020 UPF0146 V_cholerae_RfbT XdhC_C YjeF_NAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
| Seed (117) |
Full (4951) |
Representative proteomes | NCBI (3729) |
Meta (762) |
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| RP15 (344) |
RP35 (698) |
RP55 (973) |
RP75 (1192) |
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| PP/heatmap | 1 | |||||||
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| Seed (117) |
Full (4951) |
Representative proteomes | NCBI (3729) |
Meta (762) |
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|---|---|---|---|---|---|---|---|---|
| RP15 (344) |
RP35 (698) |
RP55 (973) |
RP75 (1192) |
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| Raw Stockholm | ||||||||
| Gzipped | ||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Prosite |
| Previous IDs: | G6PD; |
| Type: | Domain |
| Author: | Finn RD, Griffiths-Jones SR |
| Number in seed: | 117 |
| Number in full: | 4951 |
| Average length of the domain: | 172.30 aa |
| Average identity of full alignment: | 37 % |
| Average coverage of the sequence by the domain: | 36.68 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 183 | ||||||||||||
| Family (HMM) version: | 17 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the G6PD_N domain has been found. There are 29 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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