PDBsum entry 1qxj

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Isomerase PDB id
Jmol PyMol
Protein chains
187 a.a. *
_NI ×2
Waters ×249
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Crystal structure of native phosphoglucose isomerase from pyrococcus furiosus
Structure: Glucose-6-phosphate isomerase. Chain: a, b. Synonym: gpi, phosphoglucose isomerase, pgi, phosphohexose isomerase, phi. Engineered: yes
Source: Pyrococcus furiosus. Organism_taxid: 2261. Gene: pgia or pf0196. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
1.80Å     R-factor:   0.197     R-free:   0.249
Authors: M.K.Swan,J.T.G.Solomons,C.C.Beeson,T.Hansen,P.Schonheit, C.Davies
Key ref:
M.K.Swan et al. (2003). Structural evidence for a hydride transfer mechanism of catalysis in phosphoglucose isomerase from Pyrococcus furiosus. J Biol Chem, 278, 47261-47268. PubMed id: 12970347 DOI: 10.1074/jbc.M308603200
07-Sep-03     Release date:   09-Dec-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P83194  (G6PI_PYRFU) -  Glucose-6-phosphate isomerase
189 a.a.
187 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glucose-6-phosphate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-glucose 6-phosphate = D-fructose 6-phosphate
D-glucose 6-phosphate
= D-fructose 6-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     gluconeogenesis   2 terms 
  Biochemical function     isomerase activity     4 terms  


    Added reference    
DOI no: 10.1074/jbc.M308603200 J Biol Chem 278:47261-47268 (2003)
PubMed id: 12970347  
Structural evidence for a hydride transfer mechanism of catalysis in phosphoglucose isomerase from Pyrococcus furiosus.
M.K.Swan, J.T.Solomons, C.C.Beeson, T.Hansen, P.Schönheit, C.Davies.
In the Euryarchaeota species Pyrococcus furiosus and Thermococcus litoralis, phosphoglucose isomerase (PGI) activity is catalyzed by an enzyme unrelated to the well known family of PGI enzymes found in prokaryotes, eukaryotes, and some archaea. We have determined the crystal structure of PGI from Pyrococcus furiosus in native form and in complex with two active site ligands, 5-phosphoarabinonate and gluconate 6-phosphate. In these structures, the metal ion, which in vivo is presumed to be Fe2+, is located in the core of the cupin fold and is immediately adjacent to the C1-C2 region of the ligands, suggesting that Fe2+ is involved in catalysis rather than serving a structural role. The active site contains a glutamate residue that contacts the substrate, but, because it is also coordinated to the metal ion, it is highly unlikely to mediate proton transfer in a cis-enediol mechanism. Consequently, we propose a hydride shift mechanism of catalysis. In this mechanism, Fe2+ is responsible for proton transfer between O1 and O2, and the hydride shift between C1 and C2 is favored by a markedly hydrophobic environment in the active site. The absence of any obvious enzymatic machinery for catalyzing ring opening of the sugar substrates suggests that pyrococcal PGI has a preference for straight chain substrates and that metabolism in extreme thermophiles may use sugars in both ring and straight chain forms.
  Selected figure(s)  
Figure 4.
FIG. 4. The structure of the PfPGI in complex with PAB at 1.7 Å resolution. a, stereo view showing PAB bound to the active site region of PfPGI. Monomer B of the dimer is shown, but the contacts are essentially the same in monomer A. The electron density is a F[o] - F[c] difference map calculated from the final coordinates refined in the absence of ligand and thus represents unbiased density of PAB. The side chains of those residues surrounding the ligand are shown in ball-and-stick form in which carbons are yellow, oxygens are red, and nitrogens are blue. The metal ion atom, denoted M, is shown as an orange sphere, and water molecules are shown as red spheres. Potential hydrogen bonding and coordination contacts are shown as dashed lines. The figure was produced using PyMOL ( (32). b, diagram of the contacts made between PAB and the enzyme in which the distances are shown in Ångstroms. The inhibitor is colored green.
Figure 7.
FIG. 7. A catalytic mechanism for phosphoglucose isomerase from P. furiosus, shown here in the glucose 6-phosphate to fructose 6-phosphate direction. The substrate binds as the straight form of G6P, and O1 and O2 displace both water molecules from the coordination shell around Fe^2+. By withdrawing electron density from O2, Fe^2+ facilitates the movement of a proton from O2 to O1, creating a carbocation at C1. An atom of hydrogen in the form of a hydride then shifts from C2 to C1. A lone pair of electrons from O2 moves to form a double bond between O2 and C2, thus creating F6P. When the product leaves the active site, water molecules again occupy the coordination positions left vacant by O1 and O2. Note that, although Glu-97 is shown in this diagram, it does not play a direct role in this proposed mechanism of catalysis. Its role appears to be to counteract the positive charge of the inferred Fe^2+ ion and it does not mediate proton transfer.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 47261-47268) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19478949 G.Agarwal, M.Rajavel, B.Gopal, and N.Srinivasan (2009).
Structure-based phylogeny as a diagnostic for functional characterization of proteins with a cupin fold.
  PLoS One, 4, e5736.  
17253648 C.Roux, N.Gresh, L.E.Perera, J.P.Piquemal, and L.Salmon (2007).
Binding of 5-phospho-D-arabinonohydroxamate and 5-phospho-D-arabinonate inhibitors to zinc phosphomannose isomerase from Candida albicans studied by polarizable molecular mechanics and quantum mechanics.
  J Comput Chem, 28, 938-957.  
17337581 M.Rhimi, M.Juy, N.Aghajari, R.Haser, and S.Bejar (2007).
Probing the essential catalytic residues and substrate affinity in the thermoactive Bacillus stearothermophilus US100 L-arabinose isomerase by site-directed mutagenesis.
  J Bacteriol, 189, 3556-3563.  
16077096 A.Teplyakov, G.Obmolova, J.Toedt, M.Y.Galperin, and G.L.Gilliland (2005).
Crystal structure of the bacterial YhcH protein indicates a role in sialic acid catabolism.
  J Bacteriol, 187, 5520-5527.
PDB code: 1s4c
16256419 B.Siebers, and P.Schönheit (2005).
Unusual pathways and enzymes of central carbohydrate metabolism in Archaea.
  Curr Opin Microbiol, 8, 695-705.  
15689508 J.H.Lee, and C.J.Jeffery (2005).
The crystal structure of rabbit phosphoglucose isomerase complexed with D-sorbitol-6-phosphate, an analog of the open chain form of D-glucose-6-phosphate.
  Protein Sci, 14, 727-734.
PDB code: 1xtb
16336264 T.Hansen, B.Schlichting, J.Grötzinger, M.K.Swan, C.Davies, and P.Schönheit (2005).
Mutagenesis of catalytically important residues of cupin type phosphoglucose isomerase from Archaeoglobus fulgidus.
  FEBS J, 272, 6266-6275.  
15716432 T.Hansen, B.Schlichting, M.Felgendreher, and P.Schönheit (2005).
Cupin-type phosphoglucose isomerases (Cupin-PGIs) constitute a novel metal-dependent PGI family representing a convergent line of PGI evolution.
  J Bacteriol, 187, 1621-1631.  
16046082 T.Hansen, and P.Schönheit (2005).
Escherichia coli phosphoglucose isomerase can be substituted by members of the PGI family, the PGI/PMI family, and the cPGI family.
  FEMS Microbiol Lett, 250, 49-53.  
15938715 W.Hirano, I.Gotoh, T.Uekita, and M.Seiki (2005).
Membrane-type 1 matrix metalloproteinase cytoplasmic tail binding protein-1 (MTCBP-1) acts as an eukaryotic aci-reductone dioxygenase (ARD) in the methionine salvage pathway.
  Genes Cells, 10, 565-574.  
15103138 A.T.Cordeiro, R.Hardré, P.A.Michels, L.Salmon, L.F.Delboni, and O.H.Thiemann (2004).
Leishmania mexicana mexicana glucose-6-phosphate isomerase: crystallization, molecular-replacement solution and inhibition.
  Acta Crystallogr D Biol Crystallogr, 60, 915-919.  
15274916 H.Nishimasu, S.Fushinobu, H.Shoun, and T.Wakagi (2004).
The first crystal structure of the novel class of fructose-1,6-bisphosphatase present in thermophilic archaea.
  Structure, 12, 949-959.
PDB code: 1umg
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 code is shown on the right.