Disease relevance of Adenosine 5'-[gamma-S]triphosphate

• To define the physical basis of RecQ enzyme function, we have determined a 1.8 A resolution crystal structure of the catalytic core of Escherichia coli RecQ in its unbound form and a 2.5 A resolution structure of the core bound to the ATP analog ATPgammaS [1].
• Consistent with these effects, ATPgammaS promotes phosphorylation of tyrosine receptor kinase A, early response kinase 1/2, and p38, thereby enhancing sensitivity to nerve growth factor and accelerating neurite formation in both PC12 cells and dorsal root ganglion neurons [2].
• Similar results were obtained when ATP was substituted for ATPgammaS at 6 degrees C. Two additional peptides, derived from the phage P1 RepA protein and the E. coli HemA protein, which bear different substrate motifs, were competitive inhibitors of SsrA binding and bound to ClpA hexamers with K(A)' > 3 x 10(7) m(-1) [3].
• In this study we report that intradermal administration of ATPgammaS, a hydrolysis-resistant P2 agonist, results in an enhanced contact hypersensitivity response in mice [4].
• Furthermore, ATPgammaS enhanced the induction of delayed-type hypersensitivity to a model tumor vaccine in mice and enhanced the Ag-presenting function of Langerhans cells (LCs) in vitro [4].

High impact information on Adenosine 5'-[gamma-S]triphosphate

• Lesion bypass by pol V does not require beta,gamma-complex in the presence of non-hydrolysable ATPgammaS, indicating that an intact RecA filament may be required for translesion synthesis [5].
• Although degradation of globular proteins requires ATP hydrolysis, the PAN-20S complex with ATPgammaS translocates and degrades unfolded and denatured proteins [6].
• Treatments that prevented release of Ca2+ from intracellular stores or activation of PKA blocked ATPgammaS-stimulated changes in capacitance [7].
• Here, we show that GluR2, PICK1, NSF, and alpha-/beta-SNAPs form a complex in the presence of ATPgammaS [8].
• We report here the X-ray crystal structures of the conserved N-terminal 40 kDa fragment of hPMS2, NhPMS2, and its complexes with ATPgammaS and ADP at 1.95, 2.7 and 2.7 A resolution, respectively [9].

Chemical compound and disease context of Adenosine 5'-[gamma-S]triphosphate

• Hairpin-primed DNA replication is also observed in the presence of NS1 and the Klenow fragment of the Escherichia coli DNA polymerase I. Addition of ATPgammaS (adenosine 5'-O-(thiotriphosphate)) blocks the initiation of DNA replication but not the extension of pre-existing hairpin primers formed in the presence of NS1 only [10].
• As proved by pharmacological means, ATPgammaS toxicity apparently involves neither indirect activation of NMDA receptors, nor ectonucleotidase activities, nor nucleoside transport and intracellular purine metabolism [11].
• The method was applied to analysis of Escherichia coli RecA protein and its complexes with Mg(2+), ATPgammaS or ADP, and single-stranded DNA (ssDNA) [12].

Biological context of Adenosine 5'-[gamma-S]triphosphate

• Hepatocyte treatment with ATPgammaS, a nonhydrolyzable ATP analog, recapitulated early signaling events associated with liver regeneration-that is, rapid and transient activation of JNK signaling, induction of immediate early genes c-fos and c-jun, and activator protein-1 (AP-1) DNA-binding activity [13].
• Di- and triphosphate sites can be simultaneously occupied as judged by sequential filling of the two binding site classes with differentially radiolabeled ADP and ATPgammaS and by fluorescence resonance energy transfer between BODIPY TR- and BODIPY FL-labeled ADP and AMPPNP [14].
• Cell proliferation was increased significantly by the presence of the stable ATP analogue ATPgammaS [15].
• When p21(cip1) is added, followed by the non-hydrolyzable analog ATPgammaS to block helicase function, unwinding is inhibited, demonstrating that plasmid unwinding is specifically attributable to an ATP hydrolysis-dependent function [16].
• The effects of ATPgammaS on HIV-1 reverse transcription appeared to be indirect, resulting from disruption of virion core morphology that was evident by transmission electron microscopy [17].

Anatomical context of Adenosine 5'-[gamma-S]triphosphate

• Moreover, in vivo injection of ATPgammaS into the sciatic nerve increased growth-associated protein-43 (GAP-43), a marker for axonal growth, in wild-type but not P2Y(2)(-/-) mice [2].
• On the other hand, cAMP was generated by treatment with BzATP and ATPgammaS, but not UTP, indicating functional expression of adenylyl cyclase-coupled P2Y(11) receptors in white adipocytes [18].
• In addition, adenosine 5'-O-(thiotriphosphate) (ATPgammaS) phosphorylated only adult gizzard tissue, the only tissue that did not demonstrate a Ca(2+) sensitization [19].
• When membranes from NIH 3T3 cells stably overexpressing GC-A were incubated with ATP, AMPPNP, or ATPgammaS, only ATPgammaS dramatically potentiated ANP-dependent cyclase activity [20].
• ATPgammaS enhances the production of inflammatory mediators by a human dermal endothelial cell line via purinergic receptor signaling [21].

Associations of Adenosine 5'-[gamma-S]triphosphate with other chemical compounds

• We found that 5'-O-(3-thio)triphosphate (ATPgammaS) activation of the G protein-coupled receptor P2Y(2) in the presence of nerve growth factor leads to the colocalization and association of tyrosine receptor kinase A and P2Y(2) receptors and is required for enhanced neuronal differentiation [2].
• The nonhydrolyzable analogs of ATP, adenosine-5'-O-(3-thiotriphosphate) (ATPgammaS) and adenyl-imidodiphosphate, each stabilized the primer recognition complex containing RFC and PCNA in the absence of p21 [22].
• We have investigated several parameters characteristic of the interaction of Rad51p with ssDNA and dsDNA, particularly the effects of the nucleotide cofactors ATP and ADP and the analogs adenosine 5'-O-(thiotriphosphate) (ATPgammaS) and adenylyl-imidodiphosphate (AMP-PNP) [23].
• (iii) Nucleotidylylation was inhibited by heparin, casein, or ATPalphaS but not by ATPgammaS [24].
• Gel-filtration experiments revealed that BLM(642-1290) exists as a monomer both in solution and in its single-stranded DNA-bound form, even in the presence of Mg(2+) and ATPgammaS [25].

Gene context of Adenosine 5'-[gamma-S]triphosphate

• RFC in the ATPgammaS-activated complex was no longer displaced from the DNA by p21 [22].
• In the lysate, Sos2 and the two chimeric proteins could be stabilized by ATPgammaS [26].
• Addition of ATP or the nonhydrolyzable ATPgammaS reduces binding of the MSH2-MSH6 complex to the DNA substrates markedly [27].
• There was a significant decrease in cell number as a result of treatment with the P2X5 receptor agonist ATPgammaS (p<0.001) and the P2X7 receptor agonist BzATP (p<0.001) [28].
• Furthermore, Mg(2+)-dependent stable phosphorylation event by ATPgammaS or protein phosphatase inhibition by calyculin A abolished activation of the TRP and TRPL channels [29].

Analytical, diagnostic and therapeutic context of Adenosine 5'-[gamma-S]triphosphate

• Internal perfusion of cells with a pipette solution containing ATPgammaS was used to prevent reversibility of phosphorylation-dependent processes [30].
• Forces developed in response to Ca(2+) (6.6 microm), Ca(2+) (0.2 microm) + GTPgammaS (1 mM), or in the absence of Ca(2+) after treatment with ATPgammaS (1 mM), were of similar magnitude [31].
• In subsequent experiments in rats maintained on a low-sodium diet, we used more selective agonists in an attempt to identify the receptor subtype responsible for the effect of ATPgammaS [32].
• To gain insight into the functional architecture of ClpA in the ATPgammaS state, we have determined its structure at 12A resolution by cryo-electron microscopy [33].
• ATPgammaS-induced proliferation was demonstrated by three separate methods, detection by scintillation counting of [3H]thymidine incorporation, immunocytochemical detection of 5-bromo-2-deoxyuridine incorporation and direct counting of cell numbers [34].

References