PDBsum entry 1nsp

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protein links
Phosphotransferase PDB id
Protein chain
150 a.a. *
Waters ×81
* Residue conservation analysis
PDB id:
Name: Phosphotransferase
Title: Mechanism of phosphate transfer by nucleoside diphosphate ki ray structures of a phospho-histidine intermediate of the e from drosophila and dictyostelium
Structure: Nucleoside diphosphate kinase. Chain: a. Engineered: yes
Source: Dictyostelium discoideum. Organism_taxid: 44689
Biol. unit: Hexamer (from PQS)
2.10Å     R-factor:   0.188    
Authors: J.Janin,S.Morera,M.Chiadmi,G.Lebras,I.Lascu
Key ref:
S.Moréra et al. (1995). Mechanism of phosphate transfer by nucleoside diphosphate kinase: X-ray structures of the phosphohistidine intermediate of the enzymes from Drosophila and Dictyostelium. Biochemistry, 34, 11062-11070. PubMed id: 7669763 DOI: 10.1021/bi00035a011
18-Apr-95     Release date:   10-Jul-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P22887  (NDKC_DICDI) -  Nucleoside diphosphate kinase, cytosolic
155 a.a.
150 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.  - Nucleoside-diphosphate kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
+ nucleoside diphosphate
+ nucleoside triphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plasma membrane   7 terms 
  Biological process     macropinocytosis   18 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1021/bi00035a011 Biochemistry 34:11062-11070 (1995)
PubMed id: 7669763  
Mechanism of phosphate transfer by nucleoside diphosphate kinase: X-ray structures of the phosphohistidine intermediate of the enzymes from Drosophila and Dictyostelium.
S.Moréra, M.Chiadmi, G.LeBras, I.Lascu, J.Janin.
Nucleoside diphosphate kinase (NDP kinase) has a ping-pong mechanism with a phosphohistidine intermediate. Crystals of the enzymes from Dictyostelium discoideum and from Drosophila melanogaster were treated with phosphoramidate, and their X-ray structures were determined at 2.1 and 2.2 A resolution, respectively. The atomic models, refined to R factors below 20%, show no conformation change relative to the free proteins. In both enzymes, the active site histidine was phosphorylated on N delta, and it was the only site of phosphorylation. The phosphate group interacts with the hydroxyl group of Tyr56 and with protein-bound water molecules. Its environment is compared with that of phosphohistidines in succinyl-CoA synthetase and in phosphocarrier proteins. The X-ray structures of phosphorylated NDP kinase and of previously determined complexes with nucleoside diphosphates provide a basis for modeling the Michaelis complex with a nucleoside triphosphate, that of the phosphorylated protein with a nucleoside diphosphate, and the transition state of the phosphate transfer reaction in which the gamma-phosphate is pentacoordinated.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21347487 J.Perry, K.Koteva, and G.Wright (2011).
Receptor domains of two-component signal transduction systems.
  Mol Biosyst, 7, 1388-1398.  
20575762 H.H.Dar, and P.K.Chakraborti (2010).
Intermolecular phosphotransfer is crucial for efficient catalytic activity of nucleoside diphosphate kinase.
  Biochem J, 430, 539-549.  
20399182 N.Tanaka, P.Smith, and S.Shuman (2010).
Structure of the RNA 3'-phosphate cyclase-adenylate intermediate illuminates nucleotide specificity and covalent nucleotidyl transfer.
  Structure, 18, 449-457.
PDB code: 3kgd
20821213 S.Dharmasiri, H.M.Harrington, and N.Dharmasiri (2010).
Heat shock modulates phosphorylation status and activity of nucleoside diphosphate kinase in cultured sugarcane cells.
  Plant Cell Rep, 29, 1305-1314.  
19486691 A.Yamamura, T.Ichimura, M.Kamekura, T.Mizuki, R.Usami, T.Makino, J.Ohtsuka, K.Miyazono, M.Okai, K.Nagata, and M.Tanokura (2009).
Molecular mechanism of distinct salt-dependent enzyme activity of two halophilic nucleoside diphosphate kinases.
  Biophys J, 96, 4692-4700.
PDB code: 2zua
19387798 S.J.Annesley, and P.R.Fisher (2009).
Dictyostelium discoideum--a model for many reasons.
  Mol Cell Biochem, 329, 73-91.  
19435876 T.S.Dexheimer, S.S.Carey, S.Zuohe, V.M.Gokhale, X.Hu, L.B.Murata, E.M.Maes, A.Weichsel, D.Sun, E.J.Meuillet, W.R.Montfort, and L.H.Hurley (2009).
NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III1.
  Mol Cancer Ther, 8, 1363-1377.
PDB codes: 3bbb 3bbc 3bbf
19627098 Y.Chen, J.Jakoncic, K.A.Parker, N.Carpino, and N.Nassar (2009).
Structures of the phosphorylated and VO(3)-bound 2H-phosphatase domain of Sts-2.
  Biochemistry, 48, 8129-8135.  
  18607079 H.Wang, R.Bao, C.Jiang, Z.Yang, C.Z.Zhou, and Y.Chen (2008).
Structure of Ynk1 from the yeast Saccharomyces cerevisiae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 572-576.
PDB code: 3b54
17200862 T.Wieland (2007).
Interaction of nucleoside diphosphate kinase B with heterotrimeric G protein betagamma dimers: consequences on G protein activation and stability.
  Naunyn Schmiedebergs Arch Pharmacol, 374, 373-383.  
16957986 H.J.Hippe, and T.Wieland (2006).
High energy phosphate transfer by NDPK B/Gbetagammacomplexes--an alternative signaling pathway involved in the regulation of basal cAMP production.
  J Bioenerg Biomembr, 38, 197-203.  
16737961 J.S.Lott, B.Paget, J.M.Johnston, L.T.Delbaere, J.A.Sigrell-Simon, M.J.Banfield, and E.N.Baker (2006).
The structure of an ancient conserved domain establishes a structural basis for stable histidine phosphorylation and identifies a new family of adenosine-specific kinases.
  J Biol Chem, 281, 22131-22141.
PDB codes: 1wvq 2gl0
16788205 K.I.Varughese, I.Tsigelny, and H.Zhao (2006).
The crystal structure of beryllofluoride Spo0F in complex with the phosphotransferase Spo0B represents a phosphotransfer pretransition state.
  J Bacteriol, 188, 4970-4977.
PDB code: 2ftk
15613396 B.Pierce, W.Tong, and Z.Weng (2005).
M-ZDOCK: a grid-based approach for Cn symmetric multimer docking.
  Bioinformatics, 21, 1472-1478.  
15561724 Y.Shen, J.I.Kim, and P.S.Song (2005).
NDPK2 as a signal transducer in the phytochrome-mediated light signaling.
  J Biol Chem, 280, 5740-5749.  
15302878 S.Tiwari, K.V.Kishan, T.Chakrabarti, and P.K.Chakraborti (2004).
Amino acid residues involved in autophosphorylation and phosphotransfer activities are distinct in nucleoside diphosphate kinase from Mycobacterium tuberculosis.
  J Biol Chem, 279, 43595-43603.  
14665452 X.Lin, C.Momany, and M.Momany (2003).
SwoHp, a nucleoside diphosphate kinase, is essential in Aspergillus nidulans.
  Eukaryot Cell, 2, 1169-1177.  
12324998 M.C.Hutter, and V.Helms (2002).
The mechanism of phosphorylation of natural nucleosides and anti-HIV analogues by nucleoside diphosphate kinase is independent of their sugar substituents.
  Chembiochem, 3, 643-651.  
12383260 P.Ek, G.Pettersson, B.Ek, F.Gong, J.P.Li, and O.Zetterqvist (2002).
Identification and characterization of a mammalian 14-kDa phosphohistidine phosphatase.
  Eur J Biochem, 269, 5016-5023.  
11741981 P.Krishnan, Q.Fu, W.Lam, J.Y.Liou, G.Dutschman, and Y.C.Cheng (2002).
Phosphorylation of pyrimidine deoxynucleoside analog diphosphates: selective phosphorylation of L-nucleoside analog diphosphates by 3-phosphoglycerate kinase.
  J Biol Chem, 277, 5453-5459.  
12111975 T.Uno, M.Ueno, M.Kikuchi, and Y.Aizono (2002).
Purification and characterization of nucleoside diphosphate kinase from the brain of Bombyx mori.
  Arch Insect Biochem Physiol, 50, 147-155.  
11277918 B.Schneider, M.Babolat, Y.W.Xu, J.Janin, M.Véron, and D.Deville-Bonne (2001).
Mechanism of phosphoryl transfer by nucleoside diphosphate kinase pH dependence and role of the active site Lys16 and Tyr56 residues.
  Eur J Biochem, 268, 1964-1971.
PDB code: 1hhq
11294625 L.Cervoni, I.Lascu, Y.Xu, P.Gonin, M.Morr, M.Merouani, J.Janin, and A.Giartosio (2001).
Binding of nucleotides to nucleoside diphosphate kinase: a calorimetric study.
  Biochemistry, 40, 4583-4589.
PDB code: 1hiy
10966457 A.M.Stock, V.L.Robinson, and P.N.Goudreau (2000).
Two-component signal transduction.
  Annu Rev Biochem, 69, 183-215.  
10329774 J.E.Ladner, N.G.Abdulaev, D.L.Kakuev, M.Tordová, K.D.Ridge, and G.L.Gilliland (1999).
The three-dimensional structures of two isoforms of nucleoside diphosphate kinase from bovine retina.
  Acta Crystallogr D Biol Crystallogr, 55, 1127-1135.
PDB code: 1bhn
10375545 M.C.Pirrung (1999).
Histidine kinases and two-component signal transduction systems.
  Chem Biol, 6, R167-R175.  
  10548064 M.Lasker, C.D.Bui, P.G.Besant, K.Sugawara, P.Thai, G.Medzihradszky, and C.W.Turck (1999).
Protein histidine phosphorylation: increased stability of thiophosphohistidine.
  Protein Sci, 8, 2177-2185.  
10353838 P.Gonin, Y.Xu, L.Milon, S.Dabernat, M.Morr, R.Kumar, M.L.Lacombe, J.Janin, and I.Lascu (1999).
Catalytic mechanism of nucleoside diphosphate kinase investigated using nucleotide analogues, viscosity effects, and X-ray crystallography.
  Biochemistry, 38, 7265-7272.
PDB code: 1b99
9565562 B.Schneider, Y.W.Xu, O.Sellam, R.Sarfati, J.Janin, M.Veron, and D.Deville-Bonne (1998).
Pre-steady state of reaction of nucleoside diphosphate kinase with anti-HIV nucleotides.
  J Biol Chem, 273, 11491-11497.  
9576910 H.Käck, K.J.Gibson, Y.Lindqvist, and G.Schneider (1998).
Snapshot of a phosphorylated substrate intermediate by kinetic crystallography.
  Proc Natl Acad Sci U S A, 95, 5495-5500.
PDB codes: 1a82 1dak
9421505 J.Wittschieben, B.O.Petersen, and S.Shuman (1998).
Replacement of the active site tyrosine of vaccinia DNA topoisomerase by glutamate, cysteine or histidine converts the enzyme into a site-specific endonuclease.
  Nucleic Acids Res, 26, 490-496.  
9685345 M.Engel, M.Seifert, B.Theisinger, U.Seyfert, and C.Welter (1998).
Glyceraldehyde-3-phosphate dehydrogenase and Nm23-H1/nucleoside diphosphate kinase A. Two old enzymes combine for the novel Nm23 protein phosphotransferase function.
  J Biol Chem, 273, 20058-20065.  
9488696 S.Schaertl, M.Konrad, and M.A.Geeves (1998).
Substrate specificity of human nucleoside-diphosphate kinase revealed by transient kinetic analysis.
  J Biol Chem, 273, 5662-5669.  
9323207 C.D.Lima, M.G.Klein, and W.A.Hendrickson (1997).
Structure-based analysis of catalysis and substrate definition in the HIT protein family.
  Science, 278, 286-290.
PDB codes: 1av5 1kpe 1kpf 4fit 5fit 6fit
9305928 D.O.Lambeth, J.G.Mehus, M.A.Ivey, and B.I.Milavetz (1997).
Characterization and cloning of a nucleoside-diphosphate kinase targeted to matrix of mitochondria in pigeon.
  J Biol Chem, 272, 24604-24611.  
9384563 G.Auerbach, R.Huber, M.Grättinger, K.Zaiss, H.Schurig, R.Jaenicke, and U.Jacob (1997).
Closed structure of phosphoglycerate kinase from Thermotoga maritima reveals the catalytic mechanism and determinants of thermal stability.
  Structure, 5, 1475-1483.
PDB code: 1vpe
9168044 O.Vinogradova, P.Badola, L.Czerski, F.D.Sönnichsen, and C.R.Sanders (1997).
Escherichia coli diacylglycerol kinase: a case study in the application of solution NMR methods to an integral membrane protein.
  Biophys J, 72, 2688-2701.  
9405398 S.H.Baek, J.Y.Kwak, S.H.Lee, T.Lee, S.H.Ryu, D.J.Uhlinger, and J.D.Lambeth (1997).
Lipase activities of p37, the major envelope protein of vaccinia virus.
  J Biol Chem, 272, 32042-32049.  
9108019 Y.W.Xu, S.Moréra, J.Janin, and J.Cherfils (1997).
AlF3 mimics the transition state of protein phosphorylation in the crystal structure of nucleoside diphosphate kinase and MgADP.
  Proc Natl Acad Sci U S A, 94, 3579-3583.
PDB codes: 1kdn 2bef
9207061 Y.Xu, O.Sellam, S.Moréra, S.Sarfati, R.Biondi, M.Véron, and J.Janin (1997).
X-ray analysis of azido-thymidine diphosphate binding to nucleoside diphosphate kinase.
  Proc Natl Acad Sci U S A, 94, 7162-7165.
PDB code: 1lwx
8663370 A.Giartosio, M.Erent, L.Cervoni, S.Moréra, J.Janin, M.Konrad, and I.Lascu (1996).
Thermal stability of hexameric and tetrameric nucleoside diphosphate kinases. Effect of subunit interaction.
  J Biol Chem, 271, 17845-17851.
PDB code: 1ncl
  8732763 C.P.Ponting, and I.D.Kerr (1996).
A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues.
  Protein Sci, 5, 914-922.  
8931563 D.Deville-Bonne, O.Sellam, F.Merola, I.Lascu, M.Desmadril, and M.Véron (1996).
Phosphorylation of nucleoside diphosphate kinase at the active site studied by steady-state and time-resolved fluorescence.
  Biochemistry, 35, 14643-14650.  
8626464 J.Bourdais, R.Biondi, S.Sarfati, C.Guerreiro, I.Lascu, J.Janin, and M.Véron (1996).
Cellular phosphorylation of anti-HIV nucleosides. Role of nucleoside diphosphate kinase.
  J Biol Chem, 271, 7887-7890.  
8794735 J.E.Wedekind, P.A.Frey, and I.Rayment (1996).
The structure of nucleotidylated histidine-166 of galactose-1-phosphate uridylyltransferase provides insight into phosphoryl group transfer.
  Biochemistry, 35, 11560-11569.
PDB code: 1hxq
8910537 M.E.Huffine, and J.M.Scholtz (1996).
Energetic implications for protein phosphorylation. Conformational stability of HPr variants that mimic phosphorylated forms.
  J Biol Chem, 271, 28898-28902.  
8747457 S.Moréra, M.L.Lacombe, Y.Xu, G.LeBras, and J.Janin (1995).
X-ray structure of human nucleoside diphosphate kinase B complexed with GDP at 2 A resolution.
  Structure, 3, 1307-1314.
PDB code: 1nue
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.