Untitled

Bernard, Mark A.; Ray, Nancy B.; Olcott, Michael C.; Hendricks, Stephen P.; Mathews, Christopher K.

doi:10.1023/a:1005537013120

Cited by 48 publications

(21 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nucleoside diphosphate kinase appears to be positioned to link these two processes; for example, we have demonstrated direct associations of E. coli NDP kinase with both T4 DNA polymerase and T4 gp32, the single-strand DNA-binding protein (5). What about adenylate kinase?…”

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

“…Lu and Inouye (5) showed that adenylate kinase could catalyze the conversion of nucleoside diphosphates to triphosphates. Experiments in our laboratory (5) showed that the phosphate donor for at least some of these reactions was ADP. So, instead of catalyzing the well known reaction, 2ADP º AMP ϩ ATP, the enzyme was evidently substituting a different nucleoside diphosphate for one of the two ADPs: (d)NDP ϩ ADP º AMP ϩ (d)NTP.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Adenylate Kinase of Escherichia coli, a Component of the Phage T4 dNTP Synthetase Complex

Kim

Shen

Olcott

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Adenylate kinase, which catalyzes the reversible ATPdependent phosphorylation of AMP to ADP and dAMP to dADP, can also catalyze the conversion of nucleoside diphosphates to the corresponding triphosphates. Lu and Inouye (Lu, Q., and Inouye, M. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5720 -5725) showed that an Escherichia coli ndk mutant, lacking nucleoside diphosphate kinase, can use adenylate kinase as an alternative source of nucleoside triphosphates. 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. In terms of kinetic linkage and specific protein-protein associations, NDP kinase is an integral component of T4 dNTP synthetase, a multienzyme complex containing phage-coded enzymes, which facilitates the synthesis of dNTPs and their flow into DNA. Here we asked whether, by similar criteria, adenylate kinase of the host cell is also a specific component of the complex. Experiments involving protein affinity chromatography, immunoprecipitation, optical biosensor measurements, and glutathione S-transferase pulldowns demonstrated direct interactions between adenylate kinase and several phagecoded enzymes, as well as E. coli nucleoside diphosphate kinase. These results identify adenylate kinase as a specific component of the complex. The rate of DNA synthesis after infection of an ndk mutant was found to be about 40% of the rate seen in wild-type infection, implying that complementation of the missing NDP kinase function by adenylate kinase is fairly efficient, but that adenylate kinase becomes rate-limiting for DNA synthesis when it is the sole source of dNTPs.Adenylate kinase catalyzes the reversible ATP-dependent phosphorylation of AMP to ADP. The reaction is involved in the de novo biosynthesis of adenine nucleotides, and it is also thought to participate in adjusting adenine nucleotide levels to meet the energy demands of a cell (1). In addition, there is evidence that the enzyme in Escherichia coli participates in phospholipid biosynthesis, although the specific involvement has not been defined (2). Temperature-sensitive mutations in adk, the structural gene for adenylate kinase, cause defective phospholipid synthesis when bacteria are grown at a nonpermissive temperature (3).A novel capability for E. coli adenylate kinase was described when Lu and Inouye (4) found that the wild-type adk gene could complement a site-specific disruption of ndk, the structural gene for nucleoside diphosphate kinase. Lu and Inouye (5) showed that adenylate kinase could catalyze the conversion of nucleoside diphosphates to triphosphates. Experiments in our laboratory (5) showed that the phosphate donor for at least some of these reactions was ADP. So, instead of catalyzing the well known reaction, 2ADP º AMP ϩ ATP, the enzyme was evidently substituting a different nucleoside diphosphate for one of the two ADPs:Both NDP 1 kinase and adenylate kinase were shown, some ye...

show abstract

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Adenylate Kinase of Escherichia coli, a Component of the Phage T4 dNTP Synthetase Complex

Kim

Shen

Olcott

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…1 and while providing nucleoside triphosphates for DNA and RNA synthesis, Ndk also plays a role in maintaining the pools of cellular nucleoside triphosphates (24,25). Mutants of E. coli lacking Ndk exhibit normal growth rates but display a mutator phenotype that cannot be entirely attributed to the lack of phosphotransferase activity (26) or to an imbalance in the cellular concentrations of nucleoside triphosphates (24,27). The possibility of a defective DNA repair function in the absence of Ndk as an additional or alternative explanation for the mutator phenotype has also been considered (27,28).…”

mentioning

confidence: 99%

Molecular and Functional Interactions between Escherichia coli Nucleoside-diphosphate Kinase and the Uracil-DNA Glycosylase Ung

Goswami¹,

Yoon

Abramczyk

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Escherichia coli nucleoside-diphosphate kinase (Ndk) catalyzes nucleoside triphosphate synthesis and maintains intracellular triphosphate pools. Mutants of E. coli lacking Ndk exhibit normal growth rates but show a mutator phenotype that cannot be entirely attributed to the absence of Ndk catalytic activity or to an imbalance in cellular triphosphates. It has been suggested previously that Ndk, similar to its human counterparts, possesses nuclease and DNA repair activities, including the excision of uracil from DNA, an activity normally associated with the Ung and Mug uracil-DNA glycosylases (UDGs) in E. coli. Here we have demonstrated that recombinant Ndk purified from wild-type E. coli contains significant UDG activity that is not intrinsic, but rather, is a consequence of a direct physical and functional interaction between Ung and Ndk, although a residual amount of intrinsic UDG activity exists as well. 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. Glutathione S-transferase pulldown and far Western analyses demonstrate that the interaction also occurs at the level of purified protein, suggesting that it is specific and direct. Moreover, significant augmentation of Ung catalytic activity by Ndk was observed, suggesting that the interaction between the two enzymes is functionally relevant. These findings represent the first example of Ung interacting with another E. coli protein and also lend support to the recently discovered role of nucleoside-diphosphate kinases as regulatory components of multiprotein complexes. Escherichia coli nucleoside-diphosphate (NDP)3 kinase (NDK, EC 2.7.4.6) belongs to a large family of highly conserved oligomeric phosphate transfer enzymes consisting of 4 -6 identically folded subunits of 16 -20 kDa, each containing an active site. NDP kinases catalyze the reversible transfer of ␥-phosphates between nucleoside di-and triphosphates at very high efficiencies through an evolutionarily conserved active site histidine residue (1-3). E. coli NDP kinase is encoded by a single gene, ndk (4), whereas the genetically distinct forms of human NDP kinases are encoded by multiple genes termed NM23-H1 through H8 (5). The name NM (nonmetastatic)23 was initially accorded to the matriarch of the family, NM23-H1, on the basis of its reported action as a tissue-specific metastasis inhibitor (6). Moreover, there is evidence that NM23/NDK proteins promote tumor formation and play various roles in normal development and cellular proliferation (7,8).NM23/NDP kinases are also multifunctional in vitro. In addition to the phosphoryl transfer reactions, they can catalyze various types of DNA cleavage (9 -12) and activate transcription (13-15). The involvement of NM23 in DNA repair was initially proposed on the basis of a covalent, lysine-mediated mechanism by which NM23-H2/NDK-B ...

show abstract

“…The primary role of NDK is to maintain nucleoside triphosphates (NTPs) and their deoxy derivatives (dNTPs) pool for the synthesis of RNA and DNA and for other biosynthetic processes in bacteria to humans [4][5][6]. Besides this fundamental role in nucleotide metabolism, NDK has been implicated in many other cellular functions.…”

Section: Introductionmentioning

confidence: 99%

NUCLEOSIDE DIPHOSPHATE KINASE GENE IS EXPRESSED THROUGH MULTIPLE TRANSCRIPTS IN Mycobacterium smegmatis

KUMAR¹,

Arumugam²,

Anand³

et al. 2012

Int J of Micr Res

View full text Add to dashboard Cite

Abstract-Nucleoside diphosphate kinase, NDK, plays a vital role in maintaining pools of nucleoside triphosphates and their respective deoxynucleoside triphosphates for the synthesis of RNA and DNA. Transcriptional regulation of ndk in mycoacteria remains unknown, although modulation of ndk expression under stress conditions involving DNA and, RNA synthesis arrest and cell division arrest had been studied in several bacterial systems. Therefore, in the present study, the start sites of transcription of ndk of Mycobacterium smegmatis (Msmndk) were identified and putative promoter regions were predicted. Using transcriptional fusions of the cloned putative promoter regions to mycobacterial codon-optimised reporter gene, gfpm 2+ , promoter activity was examined under active phase of growth, nutrient starvation and other stress conditions involving DNA replication inhibition and cell division arrest. Msmndk was found to be expressed through two transcripts, T1 and T2, arising from P1 and P2 promoters, respectively. Both the promoters belonged to C group of mycobacterial promoters, which do not possess consensus to any known canonical sigma factor recognition sequences. The levels of T2, but not of T1, were found to be low under the different stress conditions studied. The data documents modulation of ndk transcripts in mycobacteria.

show abstract

Untitled

Cited by 48 publications

References 25 publications

Adenylate Kinase of Escherichia coli, a Component of the Phage T4 dNTP Synthetase Complex

Adenylate Kinase of Escherichia coli, a Component of the Phage T4 dNTP Synthetase Complex

Molecular and Functional Interactions between Escherichia coli Nucleoside-diphosphate Kinase and the Uracil-DNA Glycosylase Ung

NUCLEOSIDE DIPHOSPHATE KINASE GENE IS EXPRESSED THROUGH MULTIPLE TRANSCRIPTS IN Mycobacterium smegmatis

Contact Info

Product

Resources

About