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PDBsum entry 1dpg

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Oxidoreductase (choh(d) - NAD(p)) PDB id
1dpg
Jmol
Contents
Protein chains
485 a.a. *
Ligands
PO4 ×3
Waters ×610
* Residue conservation analysis
PDB id:
1dpg
Name: Oxidoreductase (choh(d) - NAD(p))
Title: Glucose 6-phosphate dehydrogenase from leuconostoc mesenteroides
Structure: Glucose 6-phosphate dehydrogenase. Chain: a, b. Synonym: g6pd. Engineered: yes. Mutation: yes
Source: Leuconostoc mesenteroides. Organism_taxid: 1245. Gene: g6pd. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.00Å     R-factor:   0.206     R-free:   0.257
Authors: M.J.Adams,P.Rowland,S.Gover
Key ref:
P.Rowland et al. (1994). The three-dimensional structure of glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides refined at 2.0 A resolution. Structure, 2, 1073-1087. PubMed id: 7881907 DOI: 10.1016/S0969-2126(94)00110-3
Date:
04-Dec-95     Release date:   08-Mar-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11411  (G6PD_LEUME) -  Glucose-6-phosphate 1-dehydrogenase
Seq:
Struc:
486 a.a.
485 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.49  - Glucose-6-phosphate dehydrogenase (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Pentose Phosphate Pathway (early stages)
      Reaction: D-glucose 6-phosphate + NADP+ = 6-phospho-D-glucono-1,5-lactone + NADPH
D-glucose 6-phosphate
+ NADP(+)
= 6-phospho-D-glucono-1,5-lactone
+ NADPH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   4 terms 
  Biochemical function     oxidoreductase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(94)00110-3 Structure 2:1073-1087 (1994)
PubMed id: 7881907  
 
 
The three-dimensional structure of glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides refined at 2.0 A resolution.
P.Rowland, A.K.Basak, S.Gover, H.R.Levy, M.J.Adams.
 
  ABSTRACT  
 
BACKGROUND: Glucose 6-phosphate dehydrogenase (G6PD) is the first enzyme of the pentose phosphate pathway. Normally the pathway is synthetic and NADP-dependent, but the Gram-positive bacterium Leuconostoc mesenteroides, which does not have a complete glycolytic pathway, also uses the oxidative enzymes of the pentose phosphate pathway for catabolic reactions, and selects either NAD or NADP depending on the demands for catabolic or anabolic metabolism. RESULTS: The structure of G6PD has been determined and refined to 2.0 A resolution. The enzyme is a dimer, each subunit consisting of two domains. The smaller domain is a classic dinucleotide-binding fold, while the larger one is a new beta+ alpha fold, not previously seen, with a predominantly antiparallel nine-stranded beta-sheet. There are significant structural differences in the coenzyme-binding domains of the two subunits, caused by Pro 149 which is cis in one subunit and trans in the other. CONCLUSIONS: The structure has allowed us to propose the location of the active site and the coenzyme-binding site, and suggests the role of many of the residues conserved between species. We propose that the conserved Arg46 would interact with both the adenine ring and the 2'-phosphate of NADP. Gln47, which is not conserved, may contribute to the change from NADP to dual coenzyme specificity. His178, in a nine-residue peptide conserved for all known sequences, binds a phosphate in the active site pocket. His240 is the most likely candidate for the base to oxidize the 1-hydroxyl group of the glucose 6-phosphate substrate.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. The G6PD dimer viewed from a point just off the dimer axis. Subunit A is shown in red and green in the same orientation as in Figure 2a. Subunit B is shown in magenta and blue. Drawn with MOLSCRIPT [50] and RASTER3D (E Merritt, unpublished program). Figure 5. The G6PD dimer viewed from a point just off the dimer axis. Subunit A is shown in red and green in the same orientation as in [3]Figure 2a. Subunit B is shown in magenta and blue. Drawn with MOLSCRIPT [[4]50] and RASTER3D (E Merritt, unpublished program).
Figure 8.
Figure 8. Differences between the phosphate binding sites in the two subunits. (a) In subunit A there are two well ordered phosphates, PO[4] 2000 and PO[4] 2002. (b) In subunit B, there is only one, PO[4] 2001. Conserved residues are labelled by subunit (A/B) and sequence number. Figure 8. Differences between the phosphate binding sites in the two subunits. (a) In subunit A there are two well ordered phosphates, PO[4] 2000 and PO[4] 2002. (b) In subunit B, there is only one, PO[4] 2001. Conserved residues are labelled by subunit (A/B) and sequence number.
 
  The above figures are reprinted by permission from Cell Press: Structure (1994, 2, 1073-1087) copyright 1994.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18493020 X.T.Wang, T.F.Chan, V.M.Lam, and P.C.Engel (2008).
What is the role of the second "structural" NADP+-binding site in human glucose 6-phosphate dehydrogenase?
  Protein Sci, 17, 1403-1411.  
17085636 M.Saliola, G.Scappucci, I.De Maria, T.Lodi, P.Mancini, and C.Falcone (2007).
Deletion of the glucose-6-phosphate dehydrogenase gene KlZWF1 affects both fermentative and respiratory metabolism in Kluyveromyces lactis.
  Eukaryot Cell, 6, 19-27.  
17611006 P.J.Mason, J.M.Bautista, and F.Gilsanz (2007).
G6PD deficiency: the genotype-phenotype association.
  Blood Rev, 21, 267-283.  
16469065 E.Dolezelová, M.Zurovec, M.Böhmová, and F.Sehnal (2006).
Use of two transcription starts in the G6PD gene of the bark beetle Ips typographus.
  Insect Mol Biol, 15, 25-32.  
16721657 M.Nakka, R.B.Iyer, and L.G.Bachas (2006).
Intersubunit disulfide interactions play a critical role in maintaining the thermostability of glucose-6-phosphate dehydrogenase from the hyperthermophilic bacterium Aquifex aeolicus.
  Protein J, 25, 17-21.  
15858258 M.Kotaka, S.Gover, L.Vandeputte-Rutten, S.W.Au, V.M.Lam, and M.J.Adams (2005).
Structural studies of glucose-6-phosphate and NADP+ binding to human glucose-6-phosphate dehydrogenase.
  Acta Crystallogr D Biol Crystallogr, 61, 495-504.
PDB codes: 2bh9 2bhl
12632401 C.O.Rangel-Yagui, H.Lam, D.T.Kamei, D.I.Wang, A.Pessoa, and D.Blankschtein (2003).
Glucose-6-phosphate dehydrogenase partitioning in two-phase aqueous mixed (nonionic/cationic) micellar systems.
  Biotechnol Bioeng, 82, 445-456.  
11857737 C.J.Kwok, A.C.Martin, S.W.Au, and V.M.Lam (2002).
G6PDdb, an integrated database of glucose-6-phosphate dehydrogenase (G6PD) mutations.
  Hum Mutat, 19, 217-224.  
12435510 T.Hansen, B.Schlichting, and P.Schönheit (2002).
Glucose-6-phosphate dehydrogenase from the hyperthermophilic bacterium Thermotoga maritima: expression of the g6pd gene and characterization of an extremely thermophilic enzyme.
  FEMS Microbiol Lett, 216, 249-253.  
12135480 X.T.Wang, S.W.Au, V.M.Lam, and P.C.Engel (2002).
Recombinant human glucose-6-phosphate dehydrogenase. Evidence for a rapid-equilibrium random-order mechanism.
  Eur J Biochem, 269, 3417-3424.  
11320304 C.E.Naylor, S.Gover, A.K.Basak, M.S.Cosgrove, H.R.Levy, and M.J.Adams (2001).
NADP+ and NAD+ binding to the dual coenzyme specific enzyme Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase: different interdomain hinge angles are seen in different binary and ternary complexes.
  Acta Crystallogr D Biol Crystallogr, 57, 635-648.
PDB codes: 1h93 1h94 1h9a 1h9b
11277923 J.L.Clarke, D.A.Scopes, O.Sodeinde, and P.J.Mason (2001).
Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase. A novel bifunctional enzyme in malaria parasites.
  Eur J Biochem, 268, 2013-2019.  
11717264 V.Chazalet, K.Uehara, R.A.Geremia, and C.Breton (2001).
Identification of essential amino acids in the Azorhizobium caulinodans fucosyltransferase NodZ.
  J Bacteriol, 183, 7067-7075.  
10745013 S.W.Au, S.Gover, V.M.Lam, and M.J.Adams (2000).
Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP(+) molecule and provides insights into enzyme deficiency.
  Structure, 8, 293-303.
PDB code: 1qki
10571945 E.Jablonska-Skwiecinska, I.Lewandowska, D.Plochocka, J.Topczewski, J.G.Zimowski, J.Klopocka, and B.Burzynska (1999).
Several mutations including two novel mutations of the glucose-6-phosphate dehydrogenase gene in Polish G6PD deficient subjects with chronic nonspherocytic hemolytic anemia, acute hemolytic anemia, and favism.
  Hum Mutat, 14, 477-484.  
10089300 S.W.Au, C.E.Naylor, S.Gover, L.Vandeputte-Rutten, D.A.Scopes, P.J.Mason, L.Luzzatto, V.M.Lam, and M.J.Adams (1999).
Solution of the structure of tetrameric human glucose 6-phosphate dehydrogenase by molecular replacement.
  Acta Crystallogr D Biol Crystallogr, 55, 826-834.  
10087441 Y.S.Cheng, T.K.Tang, and M.Hwang (1999).
Amino acid conservation and clinical severity of human glucose-6-phosphate dehydrogenase mutations.
  J Biomed Sci, 6, 106-114.  
  9555906 E.Purwantini, and L.Daniels (1998).
Molecular analysis of the gene encoding F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis.
  J Bacteriol, 180, 2212-2219.  
9485426 M.S.Cosgrove, C.Naylor, S.Paludan, M.J.Adams, and H.R.Levy (1998).
On the mechanism of the reaction catalyzed by glucose 6-phosphate dehydrogenase.
  Biochemistry, 37, 2759-2767.
PDB code: 2dpg
9428520 C.Kisker, H.Schindelin, A.Pacheco, W.A.Wehbi, R.M.Garrett, K.V.Rajagopalan, J.H.Enemark, and D.C.Rees (1997).
Molecular basis of sulfite oxidase deficiency from the structure of sulfite oxidase.
  Cell, 91, 973-983.
PDB code: 1sox
9341136 I.Wenderoth, R.Scheibe, and A.von Schaewen (1997).
Identification of the cysteine residues involved in redox modification of plant plastidic glucose-6-phosphate dehydrogenase.
  J Biol Chem, 272, 26985-26990.  
9290255 T.Yanase (1997).
Human genetics: past, present, and future, with special reference to major trends in Japan.
  Jpn J Hum Genet, 42, 265-316.  
8760336 G.Martini, and M.V.Ursini (1996).
A new lease of life for an old enzyme.
  Bioessays, 18, 631-637.  
8634248 J.Eyschen, B.Vitoux, S.Rahuel-Clermont, M.Marraud, G.Branlant, and M.T.Cung (1996).
Phosphorus-31 nuclear magnetic resonance studies on coenzyme binding and specificity in glyceraldehyde-3-phosphate dehydrogenase.
  Biochemistry, 35, 6064-6072.  
8994968 R.L.Kingston, R.K.Scopes, and E.N.Baker (1996).
The structure of glucose-fructose oxidoreductase from Zymomonas mobilis: an osmoprotective periplasmic enzyme containing non-dissociable NADP.
  Structure, 4, 1413-1428.
PDB code: 1ofg
8956035 T.Vulliamy, A.Rovira, N.Yusoff, D.Colomer, L.Luzzatto, and J.L.Vives-Corrons (1996).
Independent origin of single and double mutations in the human glucose 6-phosphate dehydrogenase gene.
  Hum Mutat, 8, 311-318.  
  8533762 J.S.Kaeda, G.P.Chhotray, M.R.Ranjit, J.M.Bautista, P.H.Reddy, D.Stevens, J.M.Naidu, R.P.Britt, T.J.Vulliamy, and L.Luzzatto (1995).
A new glucose-6-phosphate dehydrogenase variant, G6PD Orissa (44 Ala-->Gly), is the major polymorphic variant in tribal populations in India.
  Am J Hum Genet, 57, 1335-1341.  
7698279 L.Luzzatto (1995).
About hemoglobins, G6PD and parasites in red cells.
  Experientia, 51, 206-208.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.