Diadenosine polyphosphates: Their biological and pharmacological significance

Baxi, Mayur D.; Vishwanatha, Jamboor K.

doi:10.1016/1056-8719(94)00127-p

Cited by 78 publications

(64 citation statements)

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“…As T4 DNA ligase has similar requirements for ATP as the mammalian DNA ligases [39,40], the latter enzymes could also synthesize Np, N. This opens perspectives relating these compounds to DNA replication. In this regard, dinucleoside tetraphosphatase has been reported in the nuclei of tomato cells [42], but not in mammals; there are reports relating Ap~A or Ap:~A to cell division [1][2][3]7,23]; the capacity of synthesis of Ap:~A (and other dinucleoside polyphosphates) by a DNA ligase and the role given to the dinucleoside triphosphatase as a tumor suppressor activity could be interrelated; finally, the development of new antitumor drugs, particularly some (tri)polyphosphates derivatives, inhibitors of DNA ligases, could be envisaged. .…”

Section: Discussionmentioning

confidence: 99%

“…Ap1A and other dinucleoside polyphosphates are present in chromaffin granules of bovine adrenal medulla [10][11][12], in synaptic terminals [13] and in human blood platelets [14]. After an appropriate stimulus they are released from these storage sites to the blood and through their interaction with some still not well defined purine receptors [15][16][17][18][19] they may modulate a variety of processes such as vascular tone [20], platelet aggregation [20,21], neurotransmission [22], cell proliferation [3,7,23], etc.…”

Section: Introductionmentioning

confidence: 99%

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T4 DNA ligase synthesizes dinucleoside polyphosphates

et al. 1998

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T4 DNA iigase (EC 6.5.1.1), one of the most widely used enzymes in genetic engineering, transfers AMP from the E-AMP complex to tripolyphosphate, ADP, ATP, GTP or dATP producing p4A, Ap3A, Ap4A, Ap4G and Ap4dA, respectively. Nicked DNA competes very effectively with GTP for the synthesis of ApIG and, conversely, tripolyphosphate (or GTP) inhibits the iigation of DNA by the ligase. As T4 DNA ligase has similar requirements for ATP as the mammalian DNA ligase(s), the latter enzyme(s) could also synthesize dinucleoside polyphosphates. The present report may be related to the recent finding that human Fhit (fragile histidine triad) protein, encoded by the FHIT putative tumor suppressor gene, is a typical dinucleoside 5',5"-Pa,pa-triphosphate (Ap3A) hydrolase (EC 3.6.1.29).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

T4 DNA ligase synthesizes dinucleoside polyphosphates

et al. 1998

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“…A, zero time; B, after 60 min; C, standards. 19), and in cell differentiation and apoptosis (20). With this plethora of diverse targets, it has been difficult to assign specific mechanisms to their modes of action.…”

Section: Fig 4 Products Of the Diadenosine Pyrophosphatase Reactionmentioning

confidence: 99%

The Gene, ialA, Associated with the Invasion of Human Erythrocytes by Bartonella bacilliformis, Designates a Nudix Hydrolase Active on Dinucleoside 5′-Polyphosphates

Conyers

Bessman

1999

Journal of Biological Chemistry

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ialA, one of two genes associated with the invasion of human red blood cells by Bartonella bacilliformis, the causative agent of several diseases, has been cloned and expressed in Escherichia coli. The protein, IalA, contains an amino acid array characteristic of a family of enzymes, the Nudix hydrolases, active on a variety of nucleoside diphosphate derivatives. IalA has been purified, identified, and characterized as an enzyme catalyzing the hydrolysis of members of a class of signaling nucleotides, the dinucleoside polyphosphates, with its highest activity on adenosine 5-tetraphospho-5-adenosine (Ap 4 A), but also hydrolyzing Ap 5 A, Ap 6 A, Gp 4 G, and Gp 5 G. In each case, a pyrophosphate linkage is cleaved yielding a nucleoside triphosphate and the remaining nucleotide moiety.Bartonella bacilliformis is the only bacterium known to invade human red blood cells, and it and other species of Bartonella are responsible for several maladies, including Carrion's disease (Oroya fever, verruga peruana), cat scratch disease, trench fever, bacilliary angiomatosis, and bacilliary endocarditis (1, 2). In their studies on the invasiveness of B. bacilliformis, Mitchell and Minnick identified a two-gene locus which, when transformed into minimally invasive Escherichia coli, markedly increased their capacity to invade red blood cells in vitro (3). This report attracted our attention, because one of these two genes, ialA (for invasion-associated locus) codes for an open reading frame containing a small array of highly conserved amino acids we have called the Nudix box (4) (see Sequence 1).All 16 of the enzymes containing this Nudix signature sequence, discovered so far (see Ref. 5), catalyze the hydrolysis of nucleoside diphosphates linked to some other moiety, X, hence the acronym (see "Note Added in Proof "). The Nudix box is represented in all three kingdoms, Archaea, Prokaryota, and Eukaryota, from viruses to humans. Recent BLAST (6) searches have uncovered over 200 putative proteins containing the Nudix motif in 60 species, and we are systematically studying the members of this primordial and widely distributed family.This communication describes the cloning of ialA, and the expression, purification, and partial characterization of the invasion-associated protein, IalA, as an enzyme catalyzing the hydrolysis of dinucleoside 5Ј-polyphosphates. EXPERIMENTAL PROCEDURES MaterialsAll biochemicals were from Sigma. Enzymes used in standard cloning procedures were from Life Technologies Inc., Stratagene, or U. S. Biochemical Corp., except the Pfu DNA polymerase from Perkin-Elmer. Oligonucleotide primers were from Integrated DNA Technologies. E. coli HMS174(DE3) cells and pET11b were obtained from Novagen. E. coli HB101 cells were from our laboratory stock. pGroESL, from George H. Lorimer, DuPont, contained the groEL and groES genes, a T7 lac promoter, and a chloramphenicol resistance gene. Sephadex G-100 was from Amersham Pharmacia Biotech. MethodsCloning-The ialA gene (GenBank TM accession number L25276) from B. bacilliformis...

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“…The Ap 4 A is composed of two adenosine moieties joined in a 5-5 0 linkage by a chain of four phosphates that is ubiquitous in prokaryotic and eukaryotic cells [10]. The concentration of Ap 4 A is increased after exposure of cells to various stresses such as heat, oxidative, nutritional, and DNA damage [11].…”

Section: Introductionmentioning

confidence: 99%