PDBsum entry 1qha

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chains
903 a.a. *
GLC ×4
G6P ×4
ANP ×2
_MG ×6
Waters ×460
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Human hexokinase type i complexed with atp analogue amp-pnp
Structure: Protein (hexokinase). Chain: a, b. Engineered: yes. Other_details: complexed with atp analogue amp-pnp
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
2.25Å     R-factor:   0.208     R-free:   0.279
Authors: C.Rosano,E.Sabini,D.Deriu,M.Magnani,M.Bolognesi
Key ref:
C.Rosano et al. (1999). Binding of non-catalytic ATP to human hexokinase I highlights the structural components for enzyme-membrane association control. Structure, 7, 1427-1437. PubMed id: 10574795 DOI: 10.1016/S0969-2126(00)80032-5
11-May-99     Release date:   10-Nov-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P19367  (HXK1_HUMAN) -  Hexokinase-1
917 a.a.
903 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.  - Hexokinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + D-hexose = ADP + D-hexose 6-phosphate
Bound ligand (Het Group name = GLC)
corresponds exactly
Bound ligand (Het Group name = ANP)
matches with 81.00% similarity
D-hexose 6-phosphate
Bound ligand (Het Group name = G6P)
corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   5 terms 
  Biological process     metabolic process   13 terms 
  Biochemical function     catalytic activity     11 terms  


DOI no: 10.1016/S0969-2126(00)80032-5 Structure 7:1427-1437 (1999)
PubMed id: 10574795  
Binding of non-catalytic ATP to human hexokinase I highlights the structural components for enzyme-membrane association control.
C.Rosano, E.Sabini, M.Rizzi, D.Deriu, G.Murshudov, M.Bianchi, G.Serafini, M.Magnani, M.Bolognesi.
BACKGROUND: Hexokinase I sets the pace of glycolysis in the brain, catalyzing the ATP-dependent phosphorylation of glucose. The catalytic properties of hexokinase I are dependent on product inhibition as well as on the action of phosphate. In vivo, a large fraction of hexokinase I is bound to the mitochondrial outer membrane, where the enzyme adopts a tetrameric assembly. The mitochondrion-bound hexokinase I is believed to optimize the ATP/ADP exchange between glucose phosphorylation and the mitochondrial oxidative phosphorylation reactions. RESULTS: The crystal structure of human hexokinase I has been determined at 2.25 A resolution. The overall structure of the enzyme is in keeping with the closed conformation previously observed in yeast hexokinase. One molecule of the ATP analogue AMP-PNP is bound to each N-terminal domain of the dimeric enzyme in a surface cleft, showing specific interactions with the nucleotide, and localized positive electrostatic potential. The molecular symmetry brings the two bound AMP-PNP molecules, at the centre of two extended surface regions, to a common side of the dimeric hexokinase I molecule. CONCLUSIONS: The binding of AMP-PNP to a protein site separated from the catalytic centre of human hexokinase I can be related to the role played by some nucleotides in dissociating the enzyme from the mitochondrial membrane, and helps in defining the molecular regions of hexokinase I that are expected to be in contact with the mitochondrion. The structural information presented here is in keeping with monoclonal antibody mapping of the free and mitochondrion-bound forms of the enzyme, and with sequence analysis of hexokinases that differ in their mitochondria binding properties.
  Selected figure(s)  
Figure 2.
Figure 2. Glucose-binding site. A view of the electron density observed for the glucose and G6P molecules in the tHK-I C-terminal domain binding site (chain A). The electron density is contoured at 1.0s level. Additional residues involved in substrate/product recognition are also displayed (for further details see Table 2).
  The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 1427-1437) copyright 1999.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21315184 C.Rosano (2011).
Molecular model of hexokinase binding to the outer mitochondrial membrane porin (VDAC1): Implication for the design of new cancer therapies.
  Mitochondrion, 11, 513-519.  
18260108 P.Kuser, F.Cupri, L.Bleicher, and I.Polikarpov (2008).
Crystal structure of yeast hexokinase PI in complex with glucose: A classical "induced fit" example revised.
  Proteins, 72, 731-740.
PDB code: 3b8a
17322968 E.J.Jeong, K.Park, H.A.Joung, C.S.Lee, D.W.Seol, B.H.Chung, and M.Kim (2007).
Detection of glucose-induced conformational change in hexokinase II using fluorescence complementation assay.
  Biotechnol Lett, 29, 797-802.  
17229727 H.Nishimasu, S.Fushinobu, H.Shoun, and T.Wakagi (2007).
Crystal structures of an ATP-dependent hexokinase with broad substrate specificity from the hyperthermophilic archaeon Sulfolobus tokodaii.
  J Biol Chem, 282, 9923-9931.
PDB codes: 2e2n 2e2o 2e2p 2e2q
16855243 K.Yang, Y.Eyobo, L.A.Brand, D.Martynowski, D.Tomchick, E.Strauss, and H.Zhang (2006).
Crystal structure of a type III pantothenate kinase: insight into the mechanism of an essential coenzyme A biosynthetic enzyme universally distributed in bacteria.
  J Bacteriol, 188, 5532-5540.
PDB code: 2gtd
16166083 D.A.Skaff, C.S.Kim, H.J.Tsai, R.B.Honzatko, and H.J.Fromm (2005).
Glucose 6-phosphate release of wild-type and mutant human brain hexokinases from mitochondria.
  J Biol Chem, 280, 38403-38409.  
16233797 S.Kawai, T.Mukai, S.Mori, B.Mikami, and K.Murata (2005).
Hypothesis: structures, evolution, and ancestor of glucose kinases in the hexokinase family.
  J Biosci Bioeng, 99, 320-330.  
15016359 K.Kamata, M.Mitsuya, T.Nishimura, J.Eiki, and Y.Nagata (2004).
Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase.
  Structure, 12, 429-438.
PDB codes: 1v4s 1v4t
15466045 V.V.Lunin, Y.Li, J.D.Schrag, P.Iannuzzi, M.Cygler, and A.Matte (2004).
Crystal structures of Escherichia coli ATP-dependent glucokinase and its complex with glucose.
  J Bacteriol, 186, 6915-6927.
PDB codes: 1q18 1sz2
11512153 C.L.Verlinde, V.Hannaert, C.Blonski, M.Willson, J.J.Périé, L.A.Fothergill-Gilmore, F.R.Opperdoes, M.H.Gelb, W.G.Hol, and P.A.Michels (2001).
Glycolysis as a target for the design of new anti-trypanosome drugs.
  Drug Resist Updat, 4, 50-65.  
11114510 H.Erlandsen, E.E.Abola, and R.C.Stevens (2000).
Combining structural genomics and enzymology: completing the picture in metabolic pathways and enzyme active sites.
  Curr Opin Struct Biol, 10, 719-730.  
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.