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PDBsum entry 1hkc

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protein ligands metals links
Phosphotransferase PDB id
1hkc
Jmol
Contents
Protein chain
899 a.a. *
Ligands
BGC
PO4 ×2
Metals
__K ×2
Waters ×150
* Residue conservation analysis
PDB id:
1hkc
Name: Phosphotransferase
Title: Recombinant human hexokinase type i complexed with glucose and phosphate
Structure: D-glucose 6-phosphotransferase. Chain: a. Synonym: hexokinase i, hexokinase type i, human brain hexokinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Organ: brain. Cellular_location: cytoplasm surface of mitochondria. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Monomer (from PDB file)
Resolution:
2.80Å     R-factor:   0.174     R-free:   0.241
Authors: A.E.Aleshin,R.B.Honzatko
Key ref:
A.E.Aleshin et al. (1998). Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate. J Mol Biol, 282, 345-357. PubMed id: 9735292 DOI: 10.1006/jmbi.1998.2017
Date:
01-Jul-98     Release date:   11-Nov-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P19367  (HXK1_HUMAN) -  Hexokinase-1
Seq:
Struc:
 
Seq:
Struc:
917 a.a.
899 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.2.7.1.1  - Hexokinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + D-hexose = ADP + D-hexose 6-phosphate
ATP
+
D-hexose
Bound ligand (Het Group name = BGC)
corresponds exactly
= ADP
+ D-hexose 6-phosphate
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  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1998.2017 J Mol Biol 282:345-357 (1998)
PubMed id: 9735292  
 
 
Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate.
A.E.Aleshin, C.Zeng, H.D.Bartunik, H.J.Fromm, R.B.Honzatko.
 
  ABSTRACT  
 
Hexokinase I, the pacemaker of glycolysis in brain tissue and red blood cells, is comprised of two similar domains fused into a single polypeptide chain. The C-terminal half of hexokinase I is catalytically active, whereas the N-terminal half is necessary for the relief of product inhibition by phosphate. A crystalline complex of recombinant human hexokinase I with glucose and phosphate (2.8 A resolution) reveals a single binding site for phosphate and glucose at the N-terminal half of the enzyme. Glucose and phosphate stabilize the N-terminal half in a closed conformation. Unexpectedly, glucose binds weakly to the C-terminal half of the enzyme and does not by itself stabilize a closed conformation. Evidently a stable, closed C-terminal half requires either ATP or glucose 6-phosphate along with glucose. The crystal structure here, in conjunction with other studies in crystallography and directed mutation, puts the phosphate regulatory site at the N-terminal half, the site of potent product inhibition at the C-terminal half, and a secondary site for the weak interaction of glucose 6-phosphate at the N-terminal half of the enzyme. The relevance of crystal structures of hexokinase I to the properties of monomeric hexokinase I and oligomers of hexokinase I bound to the surface of mitochondria is discussed.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Stereoview of a single polypeptide chain in the glucose/P[i] dimer of hexokinase I. Residue 465 separates the N and C-terminal halves. The color code is as follows, yellow, small domains (residues 75 to 209, 448 to 465 and residues 523 to 657, 896 to 913); light purple, large domains (residues 13 to 74, 210 to 447 and residues 466 to 522, 658 to 895); dark purple, segments participating in intrachain salt links (residues 242 to 250, 796 to 813); blue, bound glucose; red, bound phosphate; green, bound metal ions. The view is perpendicular to the dimer 2-fold axis. Drawing made using MOLSCRIPT [Kraulis 1991].
Figure 9.
Figure 9. Superposition of a model for hexokinase I with the N-terminal half in an open conformation (bold lines) onto the glucose/P[i] complex, using the small domain of the N-terminal half as a basis for the superposition. The transition from a closed to an opened conformation moves the large domain of the N-terminal half relative to the remainder of the enzyme and should influence contacts between the N and C-terminal halves.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 282, 345-357) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21072205 E.Wyatt, R.Wu, W.Rabeh, H.W.Park, M.Ghanefar, and H.Ardehali (2010).
Regulation and cytoprotective role of hexokinase III.
  PLoS One, 5, e13823.  
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.  
18726182 P.B.Iynedjian (2009).
Molecular physiology of mammalian glucokinase.
  Cell Mol Life Sci, 66, 27-42.  
18397317 J.Molnes, L.Bjørkhaug, O.Søvik, P.R.Njølstad, and T.Flatmark (2008).
Catalytic activation of human glucokinase by substrate binding: residue contacts involved in the binding of D-glucose to the super-open form and conformational transitions.
  FEBS J, 275, 2467-2481.  
18509164 N.Nakamura, A.Miranda-Vizuete, K.Miki, C.Mori, and E.M.Eddy (2008).
Cleavage of disulfide bonds in mouse spermatogenic cell-specific type 1 hexokinase isozyme is associated with increased hexokinase activity and initiation of sperm motility.
  Biol Reprod, 79, 537-545.  
18382660 N.Tinto, A.Zagari, M.Capuano, A.De Simone, V.Capobianco, G.Daniele, M.Giugliano, R.Spadaro, A.Franzese, and L.Sacchetti (2008).
Glucokinase gene mutations: structural and genotype-phenotype analyses in MODY children from South Italy.
  PLoS ONE, 3, e1870.  
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
17873883 A.Orlova, E.C.Garner, V.E.Galkin, J.Heuser, R.D.Mullins, and E.H.Egelman (2007).
The structure of bacterial ParM filaments.
  Nat Struct Mol Biol, 14, 921-926.
PDB code: 2qu4
17965017 E.Reisler, and E.H.Egelman (2007).
Actin structure and function: what we still do not understand.
  J Biol Chem, 282, 36133-36137.  
17080299 H.J.Tsai (2007).
Function of interdomain alpha-helix in human brain hexokinase: covalent linkage and catalytic regulation between N- and C-terminal halves.
  J Biomed Sci, 14, 195-202.  
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
16938872 J.Zhang, C.Li, K.Chen, W.Zhu, X.Shen, and H.Jiang (2006).
Conformational transition pathway in the allosteric process of human glucokinase.
  Proc Natl Acad Sci U S A, 103, 13368-13373.  
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
15377666 T.Mukai, S.Kawai, S.Mori, B.Mikami, and K.Murata (2004).
Crystal structure of bacterial inorganic polyphosphate/ATP-glucomannokinase. Insights into kinase evolution.
  J Biol Chem, 279, 50591-50600.
PDB code: 1woq
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
12925806 T.Mukai, S.Kawai, S.Mori, B.Mikami, and K.Murata (2003).
Crystallization and preliminary X-ray analysis of inorganic polyphosphate/ATP-glucomannokinase from Arthrobacter sp. strain KM.
  Acta Crystallogr D Biol Crystallogr, 59, 1662-1664.  
11390360 K.Gottlob, N.Majewski, S.Kennedy, E.Kandel, R.B.Robey, and N.Hay (2001).
Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase.
  Genes Dev, 15, 1406-1418.  
10387081 A.E.Aleshin, M.Malfois, X.Liu, C.S.Kim, H.J.Fromm, R.B.Honzatko, M.H.Koch, and D.I.Svergun (1999).
Nonaggregating mutant of recombinant human hexokinase I exhibits wild-type kinetics and rod-like conformations in solution.
  Biochemistry, 38, 8359-8366.  
10574795 C.Rosano, E.Sabini, M.Rizzi, D.Deriu, G.Murshudov, M.Bianchi, G.Serafini, M.Magnani, and M.Bolognesi (1999).
Binding of non-catalytic ATP to human hexokinase I highlights the structural components for enzyme-membrane association control.
  Structure, 7, 1427-1437.
PDB code: 1qha
10347146 H.Ardehali, R.L.Printz, R.R.Whitesell, J.M.May, and D.K.Granner (1999).
Functional interaction between the N- and C-terminal halves of human hexokinase II.
  J Biol Chem, 274, 15986-15989.  
10531306 X.Liu, C.S.Kim, F.T.Kurbanov, R.B.Honzatko, and H.J.Fromm (1999).
Dual mechanisms for glucose 6-phosphate inhibition of human brain hexokinase.
  J Biol Chem, 274, 31155-31159.  
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.