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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Ndp kinase in complex with adenosine phosphonoacetic acid
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Structure:
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Nucleoside diphosphate kinase, cytosolic. Chain: a, b, c, d, e, f. Synonym: ndk, ndp kinase. Engineered: yes
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Source:
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Dictyostelium discoideum. Organism_taxid: 44689. Gene: ndkc, ndkb, gip17, dd_02290, dd_02289. Expressed in: escherichia coli. Expression_system_taxid: 562
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Biol. unit:
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Hexamer (from
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Resolution:
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2.00Å
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R-factor:
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0.187
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R-free:
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0.239
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Authors:
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Y.Chen,S.Morera,C.Pasti,A.Angusti,N.Solaroli,M.Veron, J.Janin,S.Manfredini,D.Deville-Bonne
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Key ref:
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Y.Chen
et al.
(2005).
Adenosine phosphonoacetic acid is slowly metabolized by NDP kinase.
Med Chem,
1,
529-536.
PubMed id:
DOI:
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Date:
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22-Jan-04
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Release date:
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01-Feb-05
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PROCHECK
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Headers
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References
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P22887
(NDKC_DICDI) -
Nucleoside diphosphate kinase, cytosolic
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Seq:
Struc:
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155 a.a.
150 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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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 55.00% 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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11 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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Med Chem
1:529-536
(2005)
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PubMed id:
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Adenosine phosphonoacetic acid is slowly metabolized by NDP kinase.
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Y.Chen,
S.Morera,
C.Pasti,
A.Angusti,
N.Solaroli,
M.Véron,
J.Janin,
S.Manfredini,
D.Deville-Bonne.
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ABSTRACT
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NDP kinase catalyzes the last step in the phosphorylation of nucleotides. It is
also involved in the activation by cellular kinases of nucleoside analogs used
in antiviral therapies. Adenosine phosphonoacetic acid, a close analog of ADP
already proposed as an inhibitor of ribonucleotide reductase, was found to be a
poor substrate for human NDP kinase, as well as a weak inhibitor with an
equilibrium dissociation constant of 0.6 mM to be compared to 0.025 mM for ADP.
The X-ray structure of a complex of adenosine phosphonoacetic acid and the NDP
kinase from Dictyostelium was determined to 2.0 A resolution showing that the
analog adopts a binding mode similar to ADP, but that no magnesium ion is
present at the active site. As ACP may also interfere with other cellular
kinases, its potential as a drug targeting NDP kinase or ribonucleotide
reductase is likely to be limited due to strong side effects. The design of new
molecules with a narrower specificity and a stronger affinity will benefit from
the detailed knowledge of the complex ACP-NDP kinase.
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