Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

nucleoside-diphosphate kinase By Reference

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.




• Summary
• Step 1
• Step 2
• Products

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.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial H⁺ leak.
• Identifying inhibitors of Trypanosoma cruzi nucleoside diphosphate kinase 1 as potential repurposed drugs for Chagas' disease.
• The Mitochondrial Nucleoside Diphosphate Kinase NME4 Mediates Metabolic Reprogramming and Plays a Key Role in Nonalcoholic Fatty Liver Disease Progression
• In-silico structural characterization and phylogenetic analysis of Nucleoside diphosphate kinase: A novel antiapoptotic protein of Porphyromonas gingivalis.
• Insilico structural characterization and phylogenetic analysis of Nucleoside diphosphate kinase: A novel anti-apoptotic protein of Porphyromonas gingivalis
• Genetic defects in peroxisome morphogenesis (Pex11β, dynamin-like protein 1, and nucleoside diphosphate kinase 3) affect docosahexaenoic acid-phospholipid metabolism.
• Molecular docking and simulation studies against nucleoside diphosphate kinase (NDK) of Pseudomonas aeruginosa with secondary metabolite identified by genome mining from paenibacillusehimensis.
• The Mechanism of Action of Lactoferrin - Nucleoside Diphosphate Kinase Complex in Combating Biofilm Formation.
• Crystal structure and characterization of nucleoside diphosphate kinase from Vibrio cholerae.
• The mitochondrially-localized nucleoside diphosphate kinase D (NME4) is a novel metastasis suppressor.
• Leishmania donovani secretory protein nucleoside diphosphate kinase b localizes in its nucleus and prevents ATP mediated cytolysis of macrophages.