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Phosphotransferase
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PDB id
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1ndc
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* Residue conservation analysis
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Enzyme class:
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E.C.2.7.4.6
- Nucleoside-diphosphate kinase.
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Reaction:
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ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
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ATP
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+
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nucleoside diphosphate
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=
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ADP
Bound ligand (Het Group name = )
matches with 73.33% similarity
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+
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nucleoside triphosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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plasma membrane
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6 terms
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Biological process
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cytoskeleton organization
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13 terms
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Biochemical function
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nucleotide binding
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6 terms
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DOI no:
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Biochemistry
33:9062-9069
(1994)
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PubMed id:
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X-ray structure of nucleoside diphosphate kinase complexed with thymidine diphosphate and Mg2+ at 2-A resolution.
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J.Cherfils,
S.Moréra,
I.Lascu,
M.Véron,
J.Janin.
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ABSTRACT
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We report the crystal structure of nucleoside diphosphate kinase (NDP kinase)
from Dictyostelium discoideum with thymidine diphosphate (dTDP) and Mg2+ bound
at the active site. The structure has been refined to an R-factor of 18.3% at
2-A resolution. The base stacks on the aromatic ring of Phe 64 near the protein
surface and is wedged between the side chains of Phe 64 and Val 116. The sugar
and the pyrophosphate are deeper inside the protein and make numerous H-bonds
with protein side chains. There is no backbone interaction with the nucleotide.
A Mg2+ ion bridges the alpha- and beta-phosphates and interacts with the protein
via water molecules. NDP kinase shows little specificity toward ribonucleotides
and deoxyribonucleotides. This property, required by the enzyme biological
function, can now be analyzed by comparing the crystal structures of free,
ADP-ligated, and dTDP-ligated enzymes. The most significant differences are
located in residues 60-64, which adapt their conformation to allow Phe 64 to
stack on both types of bases. Nonspecific binding is achieved by the absence of
polar interaction between the base and protein atoms. The ribose of ADP and the
deoxyribose of dTDP occupy similar positions, their hydroxyl groups interacting
with Lys 16 and Asn 119. The H-bond between Lys 16 and the O2' hydroxyl of ADP
is replaced by a similar interaction with a water molecule in the dTDP complex.
The beta-phosphate position is the same for ADP and dTDP, suggesting that the
mechanism of phosphate transfer is the same for all substrates ofNDP
kinase.(ABSTRACT TRUNCATED AT 250 WORDS)
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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|
S.J.Annesley,
and
P.R.Fisher
(2009).
Dictyostelium discoideum--a model for many reasons.
|
| |
Mol Cell Biochem, 329,
73-91.
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S.Jeudy,
A.Lartigue,
J.M.Claverie,
and
C.Abergel
(2009).
Dissecting the unique nucleotide specificity of mimivirus nucleoside diphosphate kinase.
|
| |
J Virol, 83,
7142-7150.
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PDB codes:
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M.A.Boudreau,
and
J.C.Vederas
(2007).
Synthesis and biological evaluation of nucleoside dicarboxylates as potential mimics of nucleoside diphosphates.
|
| |
Org Biomol Chem, 5,
627-635.
|
|
|
|
|
|
|
M.N.Hung,
E.Rangarajan,
C.Munger,
G.Nadeau,
T.Sulea,
and
A.Matte
(2006).
Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis.
|
| |
J Bacteriol, 188,
5606-5617.
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PDB codes:
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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.
|
|
|
|
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|
|
N.Fernandez-Fuentes,
A.Hermoso,
J.Espadaler,
E.Querol,
F.X.Aviles,
and
B.Oliva
(2004).
Classification of common functional loops of kinase super-families.
|
| |
Proteins, 56,
539-555.
|
|
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|
|
S.Gallois-Montbrun,
B.Schneider,
Y.Chen,
V.Giacomoni-Fernandes,
L.Mulard,
S.Morera,
J.Janin,
D.Deville-Bonne,
and
M.Veron
(2002).
Improving nucleoside diphosphate kinase for antiviral nucleotide analogs activation.
|
| |
J Biol Chem, 277,
39953-39959.
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PDB code:
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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.
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PDB code:
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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.
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PDB code:
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P.Petrová,
J.Koca,
and
A.Imberty
(2001).
Molecular dynamics simulations of solvated UDP-glucose in interaction with Mg2+ cations.
|
| |
Eur J Biochem, 268,
5365-5374.
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S.J.Admiraal,
P.Meyer,
B.Schneider,
D.Deville-Bonne,
J.Janin,
and
D.Herschlag
(2001).
Chemical rescue of phosphoryl transfer in a cavity mutant: a cautionary tale for site-directed mutagenesis.
|
| |
Biochemistry, 40,
403-413.
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PDB code:
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S.Raveh,
J.Vinh,
J.Rossier,
F.Agou,
and
M.Véron
(2001).
Peptidic determinants and structural model of human NDP kinase B (Nm23-H2) bound to single-stranded DNA.
|
| |
Biochemistry, 40,
5882-5893.
|
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|
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P.Meyer,
B.Schneider,
S.Sarfati,
D.Deville-Bonne,
C.Guerreiro,
J.Boretto,
J.Janin,
M.Véron,
and
B.Canard
(2000).
Structural basis for activation of alpha-boranophosphate nucleotide analogues targeting drug-resistant reverse transcriptase.
|
| |
EMBO J, 19,
3520-3529.
|
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PDB codes:
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E.H.Postel
(1999).
Cleavage of DNA by human NM23-H2/nucleoside diphosphate kinase involves formation of a covalent protein-DNA complex.
|
| |
J Biol Chem, 274,
22821-22829.
|
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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.
|
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PDB code:
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|
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.
|
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PDB code:
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|
S.J.Admiraal,
B.Schneider,
P.Meyer,
J.Janin,
M.Véron,
D.Deville-Bonne,
and
D.Herschlag
(1999).
Nucleophilic activation by positioning in phosphoryl transfer catalyzed by nucleoside diphosphate kinase.
|
| |
Biochemistry, 38,
4701-4711.
|
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PDB code:
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A.Matte,
L.W.Tari,
and
L.T.Delbaere
(1998).
How do kinases transfer phosphoryl groups?
|
| |
Structure, 6,
413-419.
|
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|
|
B.Schneider,
Y.W.Xu,
J.Janin,
M.Véron,
and
D.Deville-Bonne
(1998).
3'-Phosphorylated nucleotides are tight binding inhibitors of nucleoside diphosphate kinase activity.
|
| |
J Biol Chem, 273,
28773-28778.
|
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PDB code:
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|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
M.Eriksson,
U.Uhlin,
S.Ramaswamy,
M.Ekberg,
K.Regnström,
B.M.Sjöberg,
and
H.Eklund
(1997).
Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding.
|
| |
Structure, 5,
1077-1092.
|
|
|
PDB codes:
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|
|
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:
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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.
|
|
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PDB code:
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|
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.
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PDB code:
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A.Karlsson,
S.Mesnildrey,
Y.Xu,
S.Moréra,
J.Janin,
and
M.Véron
(1996).
Nucleoside diphosphate kinase. Investigation of the intersubunit contacts by site-directed mutagenesis and crystallography.
|
| |
J Biol Chem, 271,
19928-19934.
|
|
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PDB code:
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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.
|
|
|
|
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|
|
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.
|
|
|
|
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|
|
K.Scheffzek,
W.Kliche,
L.Wiesmüller,
and
J.Reinstein
(1996).
Crystal structure of the complex of UMP/CMP kinase from Dictyostelium discoideum and the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-uridyl) pentaphosphate (UP5A) and Mg2+ at 2.2 A: implications for water-mediated specificity.
|
| |
Biochemistry, 35,
9716-9727.
|
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PDB codes:
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M.Brodbeck,
A.Rohling,
W.Wohlleben,
C.J.Thompson,
and
U.Süsstrunk
(1996).
Nucleoside-diphosphate kinase from Streptomyces coelicolor.
|
| |
Eur J Biochem, 239,
208-213.
|
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|
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M.G.Surette,
M.Levit,
Y.Liu,
G.Lukat,
E.G.Ninfa,
A.Ninfa,
and
J.B.Stock
(1996).
Dimerization is required for the activity of the protein histidine kinase CheA that mediates signal transduction in bacterial chemotaxis.
|
| |
J Biol Chem, 271,
939-945.
|
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N.J.MacDonald,
J.M.Freije,
M.L.Stracke,
R.E.Manrow,
and
P.S.Steeg
(1996).
Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells.
|
| |
J Biol Chem, 271,
25107-25116.
|
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C.S.Poornima,
and
P.M.Dean
(1995).
Hydration in drug design. 2. Influence of local site surface shape on water binding.
|
| |
J Comput Aided Mol Des, 9,
513-520.
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L.Timmons,
J.Xu,
G.Hersperger,
X.F.Deng,
and
A.Shearn
(1995).
Point mutations in awdKpn which revert the prune/Killer of prune lethal interaction affect conserved residues that are involved in nucleoside diphosphate kinase substrate binding and catalysis.
|
| |
J Biol Chem, 270,
23021-23030.
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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.
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PDB code:
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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.
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Links
