PDBsum entry 2bhl

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Oxidoreductase PDB id
Protein chain
479 a.a. *
GOL ×6
BG6 ×2
Waters ×81
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: X-ray structure of human glucose-6-phosphate dehydrogenase (deletion variant) complexed with glucose-6-phosphate
Structure: Glucose-6-phosphate 1-dehydrogenase. Chain: a, b. Synonym: g6pd. Engineered: yes. Mutation: yes. Other_details: the 25 n-terminal residues have been removed and the first residue is valine, not histidine
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
2.90Å     R-factor:   0.214     R-free:   0.261
Authors: M.Kotaka,S.Gover,V.M.S.Lam,M.J.Adams
Key ref:
M.Kotaka et al. (2005). Structural studies of glucose-6-phosphate and NADP+ binding to human glucose-6-phosphate dehydrogenase. Acta Crystallogr D Biol Crystallogr, 61, 495-504. PubMed id: 15858258 DOI: 10.1107/S0907444905002350
13-Jan-05     Release date:   25-Apr-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P11413  (G6PD_HUMAN) -  Glucose-6-phosphate 1-dehydrogenase
515 a.a.
479 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.  - Glucose-6-phosphate dehydrogenase (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Pentose Phosphate Pathway (early stages)
      Reaction: D-glucose 6-phosphate + NADP+ = 6-phospho-D-glucono-1,5-lactone + NADPH
D-glucose 6-phosphate
Bound ligand (Het Group name = BG6)
corresponds exactly
+ NADP(+)
= 6-phospho-D-glucono-1,5-lactone
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   6 terms 
  Biological process     small molecule metabolic process   23 terms 
  Biochemical function     protein binding     7 terms  


DOI no: 10.1107/S0907444905002350 Acta Crystallogr D Biol Crystallogr 61:495-504 (2005)
PubMed id: 15858258  
Structural studies of glucose-6-phosphate and NADP+ binding to human glucose-6-phosphate dehydrogenase.
M.Kotaka, S.Gover, L.Vandeputte-Rutten, S.W.Au, V.M.Lam, M.J.Adams.
Human glucose-6-phosphate dehydrogenase (G6PD) is NADP(+)-dependent and catalyses the first and rate-limiting step of the pentose phosphate shunt. Binary complexes of the human deletion mutant, DeltaG6PD, with glucose-6-phosphate and NADP(+) have been crystallized and their structures solved to 2.9 and 2.5 A, respectively. The structures are compared with the previously determined structure of the Canton variant of human G6PD (G6PD(Canton)) in which NADP(+) is bound at the structural site. Substrate binding in DeltaG6PD is shown to be very similar to that described previously in Leuconostoc mesenteroides G6PD. NADP(+) binding at the coenzyme site is seen to be comparable to NADP(+) binding in L. mesenteroides G6PD, although some differences arise as a result of sequence changes. The tetramer interface varies slightly among the human G6PD complexes, suggesting flexibility in the predominantly hydrophilic dimer-dimer interactions. In both complexes, Pro172 of the conserved peptide EKPxG is in the cis conformation; it is seen to be crucial for close approach of the substrate and coenzyme during the enzymatic reaction. Structural NADP(+) binds in a very similar way in the DeltaG6PD-NADP(+) complex and in G6PD(Canton), while in the substrate complex the structural NADP(+) has low occupancy and the C-terminal tail at the structural NADP(+) site is disordered. The implications of possible interaction between the structural NADP(+) and G6P are considered.
  Selected figure(s)  
Figure 1.
Figure 1 The human G6PD[Canton] dimer. Helices and sheet strands of the A subunit are shown in red and green, respectively, and each of the secondary-structure elements identified in the G6PD[Canton] structure is labelled. The figure was prepared using BOBSCRIPT (Kraulis, 1991 [Kraulis, P. J. (1991). J. Appl. Cryst. 24, 946-950.]-[bluearr.gif] ; Esnouf, 1997 [Esnouf, R. M. (1997). J. Mol. Graph. 15, 132-134.]-[bluearr.gif] ) and RASTER3D (Merrit & Murphy, 1994 [Merrit, M. A. & Murphy, M. E. P. (1994). Acta Cryst. D50, 869-873.]-[bluearr.gif] ; Bacon & Anderson, 1988 [Bacon, D. J. & Anderson, W. F. (1988). J. Mol. Graph. 6, 219-220.]-[bluearr.gif] ), as were all other diagrams in this paper.
Figure 8.
Figure 8 Residues bridging from the G6P site to the structural NADP+ site The same view is used to allow comparison of this region in (a) [Delta] G6PD-G6P and (b) [Delta] G6PD-NADP+. Sheet strands are drawn in green and identified as in Fig. 1 [link]-[turqarr.gif] . Class I variants arise on mutation of those residues labelled in magenta.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2005, 61, 495-504) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19284595 X.T.Wang, and P.C.Engel (2009).
An optimised system for refolding of human glucose 6-phosphate dehydrogenase.
  BMC Biotechnol, 9, 19.  
18156501 E.Beutler (2008).
Glucose-6-phosphate dehydrogenase deficiency: a historical perspective.
  Blood, 111, 16-24.  
18029214 G.Sriram, L.Rahib, J.S.He, A.E.Campos, L.S.Parr, J.C.Liao, and K.M.Dipple (2008).
Global metabolic effects of glycerol kinase overexpression in rat hepatoma cells.
  Mol Genet Metab, 93, 145-159.  
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.  
17637841 F.Kiani, S.Schwarzl, S.Fischer, and T.Efferth (2007).
Three-dimensional modeling of glucose-6-phosphate dehydrogenase-deficient variants from German ancestry.
  PLoS ONE, 2, e625.  
17611006 P.J.Mason, J.M.Bautista, and F.Gilsanz (2007).
G6PD deficiency: the genotype-phenotype association.
  Blood Rev, 21, 267-283.  
17653668 Y.Yang, Y.Zhu, D.Li, Z.Li, H.Lü, J.Wu, J.Tang, and S.Tong (2007).
Characterization of glucose-6-phosphate dehydrogenase deficiency and identification of a novel haplotype 487G>A/IVS5-612(G>C) in the Achang population of Southwestern China.
  Sci China C Life Sci, 50, 479-485.  
16607506 W.Jiang, G.Yu, P.Liu, Q.Geng, L.Chen, Q.Lin, X.Ren, W.Ye, Y.He, Y.Guo, S.Duan, J.Wen, H.Li, Y.Qi, C.Jiang, Y.Zheng, C.Liu, E.Si, Q.Zhang, Q.Tian, and C.Du (2006).
Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population.
  Hum Genet, 119, 463-478.  
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