Disease relevance of ndk

• E. coli cells disrupted in the ndk gene display a spontaneous mutator phenotype, which has been attributed to the mutagenic effects of imbalanced nucleotide pools and errors made by replicative DNA polymerases [1].
• Bacteriophage T4 can reproduce in an Escherichia coli ndk mutant, implying that adenylate kinase can meet a demand for deoxyribonucleoside triphosphates that increases by up to 10-fold as a result of T4 infection [2].
• Dictyostelium nucleoside diphosphate kinase highly homologous to Nm23 and Awd proteins involved in mammalian tumor metastasis and Drosophila development [3].
• Characterization of nucleoside-diphosphate kinase from Pseudomonas aeruginosa: complex formation with succinyl-CoA synthetase [4].
• The N-terminal 12 amino acid sequence of P. aeruginosa Ndk shows significant homology with that of Myxococcus xanthus and that of Escherichia coli [4].

High impact information on ndk

• Properties of Drosophila NDP kinase, the product of the awd developmental gene, and of the human enzyme, the product of the nm23 genes in tumorigenesis, are discussed in view of the three-dimensional structure and of possible interactions of NDP kinase with other nucleotide binding proteins [5].
• Escherichia coli nucleoside diphosphate kinase (Ndk) catalyzes ATP-dependent synthesis of ribo- and deoxyribonucleoside triphosphates from the cognate diphosphate precursor [6].
• Escherichia coli nucleoside diphosphate kinase does not act as a uracil-processing DNA repair nuclease [6].
• The 33-kDa alpha subunit of succinyl-CoA synthetase of P. aeruginosa appears to undergo autophosphorylation in the presence of either ATP or GTP, although the presence of small amounts of Ndk activity may influence the level of such phosphorylation [4].
• Ndk enzyme activity is also associated with succinyl-CoA synthetase activity in P. aeruginosa, whose alpha and beta subunits show extensive sequence homology with those of E. coli and Dictyostelium discoideum [4].

Chemical compound and disease context of ndk

• Escherichia coli nucleoside diphosphate kinase is a uracil-processing DNA repair nuclease [1].
• Escherichia coli nucleoside-diphosphate kinase (Ndk) catalyzes nucleoside triphosphate synthesis and maintains intracellular triphosphate pools [7].
• Further studies show that NDP kinase can act as a protein kinase to phosphorylate histidine protein kinases such as EnvZ and CheA which are members of the His-Asp phosphorelay signal transduction systems in E. coli [8].
• The GST (glutathione S-transferase)-NDK (nucleoside diphosphate kinase) fusion protein was expressed in Escherichia coli [9].
• Kinetic analysis demonstrated that the irreversible inhibition of nucleoside diphosphate kinase of Escherichia coli by desdanine proceeds via a reversible Enzyme-Inhibitor complex [10].

Biological context of ndk

• However, ndk disruption unbalances the dNTP pools and stimulates mutagenesis [11].
• Sequence and characterization of the Escherichia coli genome between the ndk and gcpE genes [12].
• In support of this, five possible processed pseudogenes were identified in different DNA segments although many other NDP kinase-related genomic fragments remained to be characterized [13].
• Because the purified EF-Tu.16-kDa Ndk complex predominantly synthesizes GTP, it seems likely that this complex is a significant source of GTP for translational elongation in protein biosynthesis [14].
• Adenosine 5'-diphosphate binding and the active site of nucleoside diphosphate kinase [15].

Anatomical context of ndk

• 70 S ribosomes of P. aeruginosa predominantly synthesize GTP, which is inhibited in presence of anti-Ndk antibodies [14].
• 5) The existence of a NDPK in macrophage membranes is proven by functional, enzymatic, and immunologic criteria [16].
• Activation of the phagocyte NADPH oxidase by Rac Guanine nucleotide exchange factors in conjunction with ATP and nucleoside diphosphate kinase [16].
• Given the ubiquitous nature of Ndk in the living cell and its role in maintaining correct ratios of intracellular nucleoside triphosphates, the implications of the occurrence of these complexes have been discussed in relation to the precursor pool for cell wall biosynthesis as well as RNA/DNA synthesis [17].

Associations of ndk with chemical compounds

• The findings with ndk, lacking nucleotide diphosphate kinase, are striking [18].
• Finally, the ndk disruption strain has highly biased nucleoside triphosphate pools, including elevations of the CTP and dCTP pools of 7- and 23-fold, respectively [19].
• Co-purification of Ung and Ndk through multicolumn low pressure and nickel-nitrilotriacetic acid affinity chromatography suggests that the interaction occurs in a cellular context, as was also suggested by co-immunoprecipitation of endogenous Ung and Ndk from cellular extracts [7].
• Stereochemical courses of nucleotidyltransferase and phosphotransferase action. Uridine diphosphate glucose pyrophosphorylase, galactose-1-phosphate uridylyltransferase, adenylate kinase, and nucleoside diphosphate kinase [20].
• X-ray structure of nucleoside diphosphate kinase complexed with thymidine diphosphate and Mg2+ at 2-A resolution [21].

Analytical, diagnostic and therapeutic context of ndk

• In genomic Southern blotting using a full-length rat NDP kinase cDNA as a probe, many positively hybridized fragments were detected [13].
• Experiments involving protein affinity chromatography, immunoprecipitation, optical biosensor measurements, and glutathione S-transferase pulldowns demonstrated direct interactions between adenylate kinase and several phage-coded enzymes, as well as E. coli nucleoside diphosphate kinase [2].
• Nucleoside diphosphate kinase from bovine retina: purification, subcellular localization, molecular cloning, and three-dimensional structure [22].
• Molecular cloning, sequence determination and heterologous expression of nucleoside diphosphate kinase from Pisum sativum [23].
• Western blot analysis using anti-NDK antibody indicated that NDK in endosperm gradually decreased during 36 h of imbibition [9].

References