PDBsum entry 1dgk

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Transferase PDB id
Jmol PyMol
Protein chain
898 a.a. *
GLC ×2
ADP ×2
Waters ×94
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Mutant monomer of recombinant human hexokinase type i with glucose and adp in the active site
Structure: Hexokinase type i. Chain: n. Synonym: hk i, brain form hexokinase. Engineered: yes. Mutation: yes. Other_details: second molecule of adp is bound near the n- terminus of the polypeptide chain. The regulatory site of the n-terminal domain is occupied with glucose and phosphate. Mutations in dimer interface and the active site
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: brain. Cell: neuron. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.80Å     R-factor:   0.260     R-free:   0.308
Authors: A.E.Aleshin,X.Liu,C.Kirby,G.P.Bourenkov,H.D.Bartunik, H.J.Fromm,R.B.Honzatko
Key ref:
A.E.Aleshin et al. (2000). Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation. J Mol Biol, 296, 1001-1015. PubMed id: 10686099 DOI: 10.1006/jmbi.1999.3494
24-Nov-99     Release date:   08-Mar-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P19367  (HXK1_HUMAN) -  Hexokinase-1
917 a.a.
898 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     sperm principal piece   7 terms 
  Biological process     metabolic process   12 terms 
  Biochemical function     catalytic activity     12 terms  


DOI no: 10.1006/jmbi.1999.3494 J Mol Biol 296:1001-1015 (2000)
PubMed id: 10686099  
Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation.
A.E.Aleshin, C.Kirby, X.Liu, G.P.Bourenkov, H.D.Bartunik, H.J.Fromm, R.B.Honzatko.
Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of two structurally similar halves connected by an alpha-helix. The enzyme dimerizes at elevated protein concentrations in solution and in crystal structures; however, almost all published data reflect the properties of a hexokinase I monomer in solution. Crystal structures of mutant forms of recombinant human hexokinase I, presented here, reveal the enzyme monomer for the first time. The mutant hexokinases bind both glucose 6-phosphate and glucose with high affinity to their N and C-terminal halves, and ADP, also with high affinity, to a site near the N terminus of the polypeptide chain. Exposure of the monomer crystals to ADP in the complete absence of glucose 6-phosphate reveals a second binding site for adenine nucleotides at the putative active site (C-half), with conformational changes extending 15 A to the contact interface between the N and C-halves. The structures reveal distinct conformational states for the C-half and a rigid-body rotation of the N-half, as possible elements of a structure-based mechanism for allosteric regulation of catalysis.
  Selected figure(s)  
Figure 1.
Figure 1. Overview of (a) the ADP/Glc-monomer complex and (b) the G6P/Glc-monomer complex of hexokinase I. The large and small domains of the N and C-halves are purple and yellow, respectively. The flexible subdomain (residues 766-812) is dark purple. The side-chains of the residues 281, 283, and 284, which were altered by mutation to block dimerization, are red. ADP molecules are cyan, glucose molecules are green, the phosphate and G6P molecules are dark blue. This drawing was made with MOLSCRIPT [Kraulis 1991] and RASTER3D [Merritt and Murphy 1994].
Figure 8.
Figure 8. ADP-binding site at the N-terminal half of hexokinase I. The ball-and-stick model represents the ADP molecule. Electron density is from an omit map (2F[obs] -F[calc]), contoured at 1.4 s from the G6P/Glc complex. Donor-acceptor interactions are indicated by dotted lines.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 296, 1001-1015) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22781900 C.Adrain, and M.Freeman (2012).
New lives for old: evolution of pseudoenzyme function illustrated by iRhoms.
  Nat Rev Mol Cell Biol, 13, 489-498.  
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.  
20647599 J.Li, A.Chaudhary, S.J.Chmura, C.Pelizzari, T.Rajh, C.Wietholt, M.Kurtoglu, and B.Aydogan (2010).
A novel functional CT contrast agent for molecular imaging of cancer.
  Phys Med Biol, 55, 4389-4397.  
20159467 J.P.Vivian, P.Riedmaier, H.Ge, J.Le Nours, F.M.Sansom, M.C.Wilce, E.Byres, M.Dias, J.W.Schmidberger, P.J.Cowan, A.J.d'Apice, E.L.Hartland, J.Rossjohn, and T.Beddoe (2010).
Crystal structure of a Legionella pneumophila ecto -triphosphate diphosphohydrolase, a structural and functional homolog of the eukaryotic NTPDases.
  Structure, 18, 228-238.
PDB codes: 3aap 3aaq 3aar
  20978598 R.Senthilkumar, R.Sabarinathan, B.S.Hameed, N.Banerjee, N.Chidambarathanu, R.Karthik, and K.Sekar (2010).
FAIR: A server for internal sequence repeats.
  Bioinformation, 4, 271-275.  
19056335 D.W.Pettigrew (2009).
Amino acid substitutions in the sugar kinase/hsp70/actin superfamily conserved ATPase core of E. coli glycerol kinase modulate allosteric ligand affinity but do not alter allosteric coupling.
  Arch Biochem Biophys, 481, 151-156.  
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.  
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
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
16555088 T.J.Lampidis, M.Kurtoglu, J.C.Maher, H.Liu, A.Krishan, V.Sheft, S.Szymanski, I.Fokt, W.R.Rudnicki, K.Ginalski, B.Lesyng, and W.Priebe (2006).
Efficacy of 2-halogen substituted D-glucose analogs in blocking glycolysis and killing "hypoxic tumor cells".
  Cancer Chemother Pharmacol, 58, 725-734.  
15771780 S.Cheek, K.Ginalski, H.Zhang, and N.V.Grishin (2005).
A comprehensive update of the sequence and structure classification of kinases.
  BMC Struct Biol, 5, 6.  
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.  
15498763 A.J.Benie, A.Blume, R.R.Schmidt, W.Reutter, S.Hinderlich, and T.Peters (2004).
Characterization of ligand binding to the bifunctional key enzyme in the sialic acid biosynthesis by NMR: II. Investigation of the ManNAc kinase functionality.
  J Biol Chem, 279, 55722-55727.  
15169949 D.Krepkiy, and H.M.Miziorko (2004).
Identification of active site residues in mevalonate diphosphate decarboxylase: implications for a family of phosphotransferases.
  Protein Sci, 13, 1875-1881.  
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
12771135 T.Wada, T.Kuzuyama, S.Satoh, S.Kuramitsu, S.Yokoyama, S.Unzai, J.R.Tame, and S.Y.Park (2003).
Crystal structure of 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase, an enzyme in the non-mevalonate pathway of isoprenoid synthesis.
  J Biol Chem, 278, 30022-30027.
PDB code: 1uek
12377129 A.E.Todd, C.A.Orengo, and J.M.Thornton (2002).
Sequence and structural differences between enzyme and nonenzyme homologs.
  Structure, 10, 1435-1451.  
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.  
11877411 Z.Fu, M.Wang, D.Potter, H.M.Miziorko, and J.J.Kim (2002).
The structure of a binary complex between a mammalian mevalonate kinase and ATP: insights into the reaction mechanism and human inherited disease.
  J Biol Chem, 277, 18134-18142.
PDB code: 1kvk
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 codes are shown on the right.