Enzyme - Nucleoside-diphosphate kinase

Alternative Name(s)
  • Nucleoside diphosphokinase.
  • Nucleoside 5'-diphosphate phosphotransferase.
  • NDK.

Catalytic Activity

2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-deoxyribonucleoside 5'-triphosphate + ADP


There are no Cofactors for this Enzyme

Reaction Mechanism

    Nucleoside diphosphate kinase (NDP kinase) is responsible for phosphorylating non-adenine nucleoside diphosphates. The phosphate donor is usually ATP, but the diphosphate nucleotide substrate is non-specific for either base or ribose / deoxyribose.

    The mechanism of nucleotide binding is different from that of most other phoshokinases and nucleotide binding proteins which use a parallel beta-sheet, NDP using an anti-parallel beta-sheet. NDPK from Dictyostelium discoideum is used as a model because it is particularly easy to crystallise.

    NDPK operates using a 'ping-pong' mechanism. The gamma-phosphate of ATP is transferred to the delta-N atom of the doubly protonated His 122 of NDPK, with the delta-N proton concomitantly transferred to the gamma-phosphate. A nucleoside diphosphate binds in the active site. The phosphate group is transferred from His 122-P to the 5' hydroxyl of the ribose. Both phosphoryl transfers are dissociative SN2-like reactions, similar to the uncatalysed reaction.

    The 3' ribose / deoxyribose hydroxyl group is more catalytically important than Tyr 56 or Lys 16; in the first transfer to His 122, it hydrogen bonds to the gamma-phosphate group, forcing the substrate into a reactive conformation and stabilising the negative charge by hydrogen bonding. The enzymatic reaction can therefore be described as substrate-assisted.

    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Asn P22887 119 1ndp 119
    His P22887 122 1ndp 122
    Glu P22887 133 1ndp 133
    Lys P22887 16 1ndp 16
    Tyr P22887 56 1ndp 56
    Step Components

    overall reactant used, proton transfer, overall product formed, enzyme-substrate complex formation, intermediate formation, bimolecular nucleophilic substitution, intermediate terminated, native state of enzyme regenerated, intermediate collapse, enzyme-substrate complex cleavage

    Step 1.

    The gamma phosphate of ATP deprotonates His122. His122 then attacks the gamma phosphate of ATP in a nucleophilic substitution, releasing the ADP product.

    Step 2.

    The nucleoside diphosphate substrate attacks the phosphate of the phosphorylated His122 in a nucleophilic substitution. The released His122 then deprotonates the triphosphate giving the nucleoside triphosphate product.


    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
Probable nucleoside diphosphate kinase DDB_G0292928 Slime mold
Probable nucleoside diphosphate kinase 5 Mouse-ear cress
Nucleoside diphosphate kinase A 1 Bovine
Nucleoside diphosphate kinase, mitochondrial Human
Nucleoside diphosphate kinase 2 Douglas-fir