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Chemical Compound Review

AC1L9G7M     [[[(2R,3R,4R,5R)-5-(6- aminopurin-9-yl)-3,4...

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Disease relevance of ATP-gamma-S

  • The ATP-gamma-S bound and unbound crystal structures of the vaccinia polymerase reveal an unusual architecture for VP55 that comprises of N-terminal, central or catalytic, and C-terminal domains with different topologies and that differs from many polymerases, including the eukaryotic poly(A) polymerases [1].
  • The ATP gamma S inhibition of AVP-stimulated adenylate cyclase activity is not affected by pertussis toxin but is attenuated by GDP beta S, suggesting a possible role for a pertussis toxin insensitive G protein in the inhibition [2].
  • Adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) will substitute for ATP in the formation of an initiation complex between the DNA polymerase III holoenzyme of Escherichia coli and primed DNA [3].
  • When DNA translocation is interrupted by the addition of ATP-gamma-S, packaged DNA exists at 0 degrees C as well as at 20 degrees C but the exit of DNA stops after one-third of the genome is inside the capsid [4].
  • In the human breast cancer cell line MCF-7, the nucleotides ATP gamma S and UTP, acting extracellularly through the purinergic receptor P2Y(2), lead to elevated intracellular calcium levels and increased proliferation [5].

High impact information on ATP-gamma-S

  • Upon ATP gamma S-induced dissociation, the leading strand polymerase is refractory to disassembly allowing cycling to occur exclusively on the lagging strand [6].
  • We demonstrate that the nonhydrolyzable ATP analog, ATP gamma S, supports the formation of an isolable leading strand complex that loads and replicates the lagging strand only in the presence of ATP, beta, and the single-stranded DNA binding protein [6].
  • ATP gamma S substituted for ATP in PKA phosphorylation, but it did not open the channel [7].
  • Hydrolysis of ATP is implicated in establishing the differential distribution of Mu B protein between immune and non-immune DNA molecules in the presence of Mu A protein; nonhydrolyzable ATP gamma S can support an efficient strand-transfer reaction even with a target DNA that is immune in a reaction with ATP [8].
  • This property is kinesin-like; however, the motility is blocked by 5 microM vanadate, 1 mM N-ethyl maleimide, 0.5 mM ATP-gamma-S, or by ATP-vanadate-UV cleavage of the 400 kd polypeptide, characteristics that differ from kinesin [9].

Chemical compound and disease context of ATP-gamma-S


Biological context of ATP-gamma-S

  • Inasmuch as hydrolysis of ATP is far slower than these initiation reactions and since the poorly hydrolyzable analogue ATP gamma S can replace ATP, the ATP function appears to be allosteric [11].
  • Our data suggest that ATP gamma S irreversibly inhibits exocytosis via thiophosphorylation of proteins associated with the egg cortex [12].
  • DNA fragmentation can be set off by ATP but not the nonhydrolysable analogue ATP gamma S nor other nucleoside-5'-triphosphates [13].
  • ATP, GTP, or ATP-gamma-S added in the PM 4-7 min later restarted anaphase A while kinetochore fibers shortened [14].
  • The hydrolysis of ATP by both polypeptides was fully inhibited by an excess of ATP gamma S and partially inhibited by ADP and 5'-adenylylimidodiphosphate, suggesting that adenine nucleotides display different affinities for the ATP binding site of chaperonins [15].

Anatomical context of ATP-gamma-S


Associations of ATP-gamma-S with other chemical compounds


Gene context of ATP-gamma-S

  • This structural rearrangement is dependent on the hydrolysis of ATP, since ATP gamma S, a competitive inhibitor of the PRP16 ATPase activity, does not promote the protection of the 3' splice site and formation of mRNA [24].
  • BiP dissociates from the complex when the purification is performed in the presence of ATP gamma S or when the starting membranes are from yeast containing the sec63-1 mutation [25].
  • ATP, but not nonhydrolyzable ATP-gamma S, regulates the SODD binding by Hsp70 or TNFR1 [26].
  • ATP gamma S and Cdc2 kinase were used to produce an RNA polymerase IIO that was not detectably dephosphorylated in the transcription extract [27].
  • Co-stimulation of CHO-A1 cells with ATP gamma S and CCK-8 produced additive increases in [3H]inositol phosphate accumulation [28].

Analytical, diagnostic and therapeutic context of ATP-gamma-S

  • Using a topological assay, we demonstrate that hRad51 underwinds duplex DNA, in a reaction dependent upon the presence of ATP or its non-hydrolysable analogue ATP gamma S. Complexes formed with single- and double-stranded DNA have been observed by electron microscopy following negative staining [29].
  • In the presence of 1 mM ATP gamma S and calcium, myosin was retained (70%) and was localized by indirect immunofluorescence in bright central spots that also stained intensely for F-actin [30].
  • The initiation complex formed in the presence of ATP gamma S between the DNA polymerase III holoenzyme and single-stranded DNA-binding protein-encoated primed M13 Gori DNA is stabile and isolable by gel filtration at room temperature [3].
  • By confocal microscopy we demonstrate that ATP gamma S increased the nucleo cytoplasmic shuttling of HuR and caused an increase in the cytosolic HuR level as shown by cell fractionation experiments [31].
  • P2-purinergic stimulation of the L-type Ca current induced by the external application of 100 microM ATP gamma S was investigated in rat ventricular cardiomyocytes using the whole-cell patch-clamp technique [32].


  1. Crystal structures of the vaccinia virus polyadenylate polymerase heterodimer: insights into ATP selectivity and processivity. Moure, C.M., Bowman, B.R., Gershon, P.D., Quiocho, F.A. Mol. Cell (2006) [Pubmed]
  2. ATP receptor regulation of adenylate cyclase and protein kinase C activity in cultured renal LLC-PK1 cells. Anderson, R.J., Breckon, R., Dixon, B.S. J. Clin. Invest. (1991) [Pubmed]
  3. Adenosine 5'-O-(3-thiotriphosphate) can support the formation of an initiation complex between the DNA polymerase III holoenzyme and primed DNA. Johanson, K.O., McHenry, C.S. J. Biol. Chem. (1984) [Pubmed]
  4. Characterization of the bacteriophage T3 DNA packaging reaction in vitro in a defined system. Shibata, H., Fujisawa, H., Minagawa, T. J. Mol. Biol. (1987) [Pubmed]
  5. Extracellular ATP activates multiple signalling pathways and potentiates growth factor-induced c-fos gene expression in MCF-7 breast cancer cells. Wagstaff, S.C., Bowler, W.B., Gallagher, J.A., Hipskind, R.A. Carcinogenesis (2000) [Pubmed]
  6. The DNA polymerase III holoenzyme: an asymmetric dimeric replicative complex with leading and lagging strand polymerases. Glover, B.P., McHenry, C.S. Cell (2001) [Pubmed]
  7. Nucleoside triphosphates are required to open the CFTR chloride channel. Anderson, M.P., Berger, H.A., Rich, D.P., Gregory, R.J., Smith, A.E., Welsh, M.J. Cell (1991) [Pubmed]
  8. Target immunity of Mu transposition reflects a differential distribution of Mu B protein. Adzuma, K., Mizuuchi, K. Cell (1988) [Pubmed]
  9. Identification of a microtubule-based cytoplasmic motor in the nematode C. elegans. Lye, R.J., Porter, M.E., Scholey, J.M., McIntosh, J.R. Cell (1987) [Pubmed]
  10. The neuronal transport mechanism for noradrenaline is not influenced by the ATP analogue ATP gamma S. Gliese, M., Babin-Ebell, J., Schömig, E., Russ, H. Life Sci. (1994) [Pubmed]
  11. ATP activates dnaA protein in initiating replication of plasmids bearing the origin of the E. coli chromosome. Sekimizu, K., Bramhill, D., Kornberg, A. Cell (1987) [Pubmed]
  12. Phosphoprotein inhibition of calcium-stimulated exocytosis in sea urchin eggs. Whalley, T., Crossley, I., Whitaker, M. J. Cell Biol. (1991) [Pubmed]
  13. Extracellular ATP as a trigger for apoptosis or programmed cell death. Zheng, L.M., Zychlinsky, A., Liu, C.C., Ojcius, D.M., Young, J.D. J. Cell Biol. (1991) [Pubmed]
  14. On the mechanism of anaphase A: evidence that ATP is needed for microtubule disassembly and not generation of polewards force. Spurck, T.P., Pickett-Heaps, J.D. J. Cell Biol. (1987) [Pubmed]
  15. A mutation in GroEL interferes with protein folding by reducing the rate of discharge of sequestered polypeptides. Baneyx, F., Gatenby, A.A. J. Biol. Chem. (1992) [Pubmed]
  16. Assembly of ER-associated protein degradation in vitro: dependence on cytosol, calnexin, and ATP. McCracken, A.A., Brodsky, J.L. J. Cell Biol. (1996) [Pubmed]
  17. Formyl peptide stimulates and ATP gamma S potentiates [3H]cytidine 5'-diphosphate diglyceride accumulation in human neutrophils. Stubbs, E.B., Walker, B.A., Owens, C.A., Ward, P.A., Agranoff, B.W. J. Immunol. (1992) [Pubmed]
  18. Thiophosphorylation of the 130-kDa subunit is associated with a decreased activity of myosin light chain phosphatase in alpha-toxin-permeabilized smooth muscle. Trinkle-Mulcahy, L., Ichikawa, K., Hartshorne, D.J., Siegman, M.J., Butler, T.M. J. Biol. Chem. (1995) [Pubmed]
  19. Homologous pairing in genetic recombination: complexes of recA protein and DNA. Shibata, T., Cunningham, R.P., DasGupta, C., Radding, C.M. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  20. P2-purinoceptor activation stimulates phosphoinositide hydrolysis and inhibits accumulation of cAMP in cultured ventricular myocytes. Yamada, M., Hamamori, Y., Akita, H., Yokoyama, M. Circ. Res. (1992) [Pubmed]
  21. Binding of ATP to eukaryotic initiation factor 2. Differential modulation of mRNA-binding activity and GTP-dependent binding of methionyl-tRNAMetf. Gonsky, R., Lebendiker, M.A., Harary, R., Banai, Y., Kaempfer, R. J. Biol. Chem. (1990) [Pubmed]
  22. Nucleoside triphosphate requirements for superoxide generation and phosphorylation in a cell-free system from human neutrophils. Sodium dodecyl sulfate and diacylglycerol activate independently of protein kinase C. Uhlinger, D.J., Burnham, D.N., Lambeth, J.D. J. Biol. Chem. (1991) [Pubmed]
  23. Thiophosphorylation causes Ca2+-independent norepinephrine secretion from permeabilized PC12 cells. Wagner, P.D., Vu, N.D. J. Biol. Chem. (1989) [Pubmed]
  24. A conformational rearrangement in the spliceosome is dependent on PRP16 and ATP hydrolysis. Schwer, B., Guthrie, C. EMBO J. (1992) [Pubmed]
  25. A Sec63p-BiP complex from yeast is required for protein translocation in a reconstituted proteoliposome. Brodsky, J.L., Schekman, R. J. Cell Biol. (1993) [Pubmed]
  26. Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain. Miki, K., Eddy, E.M. Mol. Cell. Biol. (2002) [Pubmed]
  27. Phosphorylation of the carboxy-terminal repeat domain in RNA polymerase II by cyclin-dependent kinases is sufficient to inhibit transcription. Gebara, M.M., Sayre, M.H., Corden, J.L. J. Cell. Biochem. (1997) [Pubmed]
  28. Synergistic interactions between human transfected adenosine A1 receptors and endogenous cholecystokinin receptors in CHO cells. Dickenson, J.M., Hill, S.J. Eur. J. Pharmacol. (1996) [Pubmed]
  29. Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA. Benson, F.E., Stasiak, A., West, S.C. EMBO J. (1994) [Pubmed]
  30. Formation and contraction of a microfilamentous shell in saponin-permeabilized platelets. Stark, F., Golla, R., Nachmias, V.T. J. Cell Biol. (1991) [Pubmed]
  31. ATP potentiates interleukin-1 beta-induced MMP-9 expression in mesangial cells via recruitment of the ELAV protein HuR. Huwiler, A., Akool, e.l.-.S., Aschrafi, A., Hamada, F.M., Pfeilschifter, J., Eberhardt, W. J. Biol. Chem. (2003) [Pubmed]
  32. A Gs protein couples P2-purinergic stimulation to cardiac Ca channels without cyclic AMP production. Scamps, F., Rybin, V., Puceat, M., Tkachuk, V., Vassort, G. J. Gen. Physiol. (1992) [Pubmed]
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