PDBsum entry 1glk

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Transferase(hexokinase) PDB id
Protein chain
458 a.a.
Theoretical model
PDB id:
Name: Transferase(hexokinase)
Structure: Glucokinase (atp:d-hexose 6-phosphotransferase) (theoretical model)
Source: Human (homo sapiens) beta-cell
Authors: R.St.Charles,R.W.Harrison,G.I.Bell,S.J.Pilkis,I.T.Weber
Key ref: R.St Charles et al. (1994). Molecular model of human beta-cell glucokinase built by analogy to the crystal structure of yeast hexokinase B. Diabetes, 43, 784-791. PubMed id: 8194664
07-Jun-94     Release date:   30-Nov-94    
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Protein chain
No UniProt id for this chain
Struc: 458 a.a.
Key:    Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.  - Hexokinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + D-hexose = ADP + D-hexose 6-phosphate
+ D-hexose
D-hexose 6-phosphate
Bound ligand (Het Group name = GLC)
matches with 75.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


Diabetes 43:784-791 (1994)
PubMed id: 8194664  
Molecular model of human beta-cell glucokinase built by analogy to the crystal structure of yeast hexokinase B.
R.St Charles, R.W.Harrison, G.I.Bell, S.J.Pilkis, I.T.Weber.
Recent studies have shown that mutations in human beta-cell glucokinase that impair the activity of this key regulatory enzyme of glycolysis can cause early-onset non-insulin-dependent diabetes mellitus (NIDDM). The amino acid sequence of human glucokinase has 31% identity with yeast hexokinase, a related enzyme for which the crystal structure has been determined. This homology has allowed us to model the three-dimensional structure of human glucokinase by analogy to the crystal structure of yeast hexokinase B. This model of human glucokinase provides a basis for understanding the effects of mutations on its enzymatic activity. Residues in the active site and on the surface of the binding cleft for glucose are highly conserved in both enzymes. Regions far from the active site are predicted to differ in conformation, and 10 insertions or deletions that range in size from 1 to 7 residues are located on the protein surface between elements of secondary structure. The model structure suggests that human glucokinase binds glucose in a similar manner to yeast hexokinase. The glucose-binding site contains a conserved aspartic acid, two conserved glutamic acids, and two conserved asparagines that form hydrogen bond interactions with the hydroxyls of the glucose similar to those observed in other sugar-binding proteins. Mutation of residues in the predicted glucose-binding site has been found to greatly reduce enzymatic activity. This model will be useful for future structure/function studies of glucokinase.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19617908 J.Zhang, C.Li, T.Shi, K.Chen, X.Shen, and H.Jiang (2009).
Lys169 of human glucokinase is a determinant for glucose phosphorylation: implication for the atomic mechanism of glucokinase catalysis.
  PLoS One, 4, e6304.  
19553681 M.A.Currie, F.Merino, T.Skarina, A.H.Wong, A.Singer, G.Brown, A.Savchenko, A.Caniuguir, V.Guixé, A.F.Yakunin, and Z.Jia (2009).
ADP-dependent 6-phosphofructokinase from Pyrococcus horikoshii OT3: structure determination and biochemical characterization of PH1645.
  J Biol Chem, 284, 22664-22671.  
14517946 A.L.Gloyn (2003).
Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.
  Hum Mutat, 22, 353-362.  
12199699 M.Berger, H.Chen, W.Reutter, and S.Hinderlich (2002).
Structure and function of N-acetylglucosamine kinase. Identification of two active site cysteines.
  Eur J Biochem, 269, 4212-4218.  
11571755 I.Mayordomo, and P.Sanz (2001).
Human pancreatic glucokinase (GlkB) complements the glucose signalling defect of Saccharomyces cerevisiae hxk2 mutants.
  Yeast, 18, 1309-1316.  
11447598 I.Mayordomo, and P.Sanz (2001).
Hexokinase PII: structural analysis and glucose signalling in the yeast Saccharomyces cerevisiae.
  Yeast, 18, 923-930.  
8856049 H.Panneman, G.J.Ruijter, H.C.van den Broeck, E.T.Driever, and J.Visser (1996).
Cloning and biochemical characterisation of an Aspergillus niger glucokinase. Evidence for the presence of separate glucokinase and hexokinase enzymes.
  Eur J Biochem, 240, 518-525.  
8897004 M.Veiga-da-Cunha, L.Z.Xu, Y.H.Lee, D.Marotta, S.J.Pilkis, and E.Van Schaftingen (1996).
Effect of mutations on the sensitivity of human beta-cell glucokinase to liver regulatory protein.
  Diabetologia, 39, 1173-1179.  
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