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Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism

Davies, Oluwafemi;Mendes, Pedro;Smallbone, Kieran;Malys, Naglis

  • Received : 2011.08.31
  • Accepted : 2011.10.04
  • Published : 2012.04.30

Abstract

Accumulation of modified nucleotides is defective to various cellular processes, especially those involving DNA and RNA. To be viable, organisms possess a number of (deoxy)nucleotide phosphohydrolases, which hydrolyze these nucleotides removing them from the active NTP and dNTP pools. Deamination of purine bases can result in accumulation of such nucleotides as ITP, dITP, XTP and dXTP. E. coli RdgB has been characterised as a deoxyribonucleoside triphosphate pyrophosphohydrolase that can act on these nucleotides. S. cerevisiae homologue encoded by YJR069C was purified and its (d)NTPase activity was assayed using fifteen nucleotide substrates. ITP, dITP, and XTP were identified as major substrates and kinetic parameters measured. Inhibition by ATP, dATP and GTP were established. On the basis of experimental and published data, modelling and simulation of ITP, dITP, XTP and dXTP metabolism was performed. (d)ITP/(d)XTPase is a new example of enzyme with multiple substrate-specificity demonstrating that multispecificity is not a rare phenomenon

Keywords

Deamination;Mathematical modelling;Nucleoside triphosphate pyrophosphatase;Purine;S. cerevisiae

References

  1. Sancar, A. and Sancar, G. B. (1988). DNA repair enzymes. Ann. Rev. Biochem. 57, 29-67. https://doi.org/10.1146/annurev.bi.57.070188.000333
  2. Nguyen, T., Brunson, D., Crespi, C. L., Penman, B. W., Wishnok, J. S. and Tannenbaum, S. R. (1992). DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc. Nat. Acad. Sci. U.S.A. 89, 3030-3034. https://doi.org/10.1073/pnas.89.7.3030
  3. Nakabeppu, Y., Sakumi, K., Sakamoto, K., Tsuchimoto, D., Tsuzuki, T. and Nakatsu, Y. (2006). Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids. Biol. Chem. 387, 373-379. https://doi.org/10.1515/BC.2006.050
  4. Nakabeppu, Y., Tsuchimoto, D., Yamaguchi, H. and Sakumi, K. (2007). Oxidative damage in nucleic acids and Parkinson's disease. J. Neurosci. Res. 85, 919-934. https://doi.org/10.1002/jnr.21191
  5. Rai, P., Onder, T. T., Young, J. J., McFaline, J. L., Pang, B., Dedon, P. C. and Weinberg, R. A. (2009). Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence. Proc. Nat. Acad. Sci. U.S.A. 106, 169-174. https://doi.org/10.1073/pnas.0809834106
  6. Kong, Q. and Lin, C. L. (2010). Oxidative damage to RNA: mechanisms, consequences and diseases. Cell. Mol. Life Sci. 67, 1817-1829. https://doi.org/10.1007/s00018-010-0277-y
  7. Iyama, T., Abolhassani, N., Tsuchimoto, D., Nonaka, M. and Nakabeppu, Y. (2010). NUDT16 is a (deoxy)inosine diphosphatase and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest. Nucleic Acids Res. 38, 4834-4843. https://doi.org/10.1093/nar/gkq249
  8. Sakumi, K., Abolhassani, N., Behmanesh, M., Iyama, T., Tsuchimoto, D. and Nakabeppu, Y. (2010). ITPA protein, an enzyme that eliminates deaminated purine nucleoside triphosphates in cells. Mutation Res. 703, 43-50. https://doi.org/10.1016/j.mrgentox.2010.06.009
  9. Burgis, N. E. and Cunningham, R. P. (2007). Substrate specificity of RdgB protein, a deoxyribonucleoside triphosphate pyrophosphohydrolase. J. Biol. Chem. 282, 3531-3538.
  10. Savchenko, A., Proudfoot, M., Skarina, T., Singer, A., Litvinova, O., Sanishvili, R., Brown, G., Chirgadze, N. and Yakunin, A. F. (2007). Molecular basis of the antimutagenic activity of the house-cleaning inosine triphosphate pyrophosphatase RdgB from Escherichia coli. J. Mol. Biol. 374, 1091-1103. https://doi.org/10.1016/j.jmb.2007.10.012
  11. Noskov, V. N., Staak, K., Shcherbakova, P. V., Kozmin, S. G., Negishi, K., Ono, B. C., Hayatsu, H. and Pavlov, Y. I. (1996). HAM 1, the gene controlling 6-N-hydroxylaminopurine sensitivity and mutagenesis in the yeast Saccharomyces cerevisiae. Yeast 12, 17-29. https://doi.org/10.1002/(SICI)1097-0061(199601)12:1<17::AID-YEA875>3.0.CO;2-I
  12. Bochnert, B. R. and Ames, B. N. (1982). Complete analysis of cellular nucleotides by two-dimensional thin layer chromatography. J. Biol. Chem. 257, 9759-9769.
  13. Vanderheiden, B. S. (1970). Human erythrocyte "ITPase": an ITP pyrophosphohydrolase. Biochim. Biophys. Acta 215, 555-558. https://doi.org/10.1016/0304-4165(70)90109-1
  14. Rafty, L. A., Schmidt, M. T., Perraud, A. L., Scharenberg, A. M. and Denu, J. M. (2002). Analysis of O-acetyl-ADP-ribose as a target for Nudix ADP-ribose hydrolases. J. Biol. Chem. 277, 47114-47122. https://doi.org/10.1074/jbc.M208997200
  15. Gadsden, M. H., McIntosh, E. M., Game, J. C., Wilson, P. J. and Haynes, R. H. (1993). dUTP pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae. EMBO J. 12, 4425-4431.
  16. Tchigvintsev, A., Singer, A. U., Flick, R., Petit, P., Brown, G., Evdokimova, E., Savchenko, A. and Yakunin, A. F. (2011). Structure and activity of the Saccharomyces cerevisiae dUTP pyrophosphatase DUT1, an essential housekeeping enzyme. Biochem. J. 437, 243-253. https://doi.org/10.1042/BJ20110304
  17. Kennedy, E. J., Pillus, L. and Ghosh, G. (2005). Pho5p and newly identified nucleotide pyrophosphatases/phosphodiesterases regulate extracellular nucleotide phosphate metabolism in Saccharomyces cerevisiae. Eukaryot. Cell 4, 1892-1901. https://doi.org/10.1128/EC.4.11.1892-1901.2005
  18. Malys N., Carroll, K., Miyan, J., Tollervey, D. and McCarthy, J. E. (2004). The 'scavenger' m7GpppX pyrophosphatase activity of Dcs1 modulates nutrient-induced responses in yeast. Nucleic Acids Res. 32, 3590-3600. https://doi.org/10.1093/nar/gkh687
  19. Malys N. and McCarthy, J. E. (2006) Dcs2, a novel stress-induced modulator of m7GpppX pyrophosphatase activity that locates to P bodies. J. Mol. Biol. 363, 370-382. https://doi.org/10.1016/j.jmb.2006.08.015
  20. Keesey, J. K. Jr, Bigelis, R. and Fink, G. R. (1979). The product of the his4 gene cluster in Saccharomyces cerevisiae. A trifunctional polypeptide. J. Biol. Chem. 254, 7427-7433.
  21. Galperin, M. Y., Moroz, O. V., Wilson, K. S. and Murzin, A. G. (2006). House cleaning, a part of good housekeeping. Mol. Microbiol. 59, 5-19. https://doi.org/10.1111/j.1365-2958.2005.04950.x
  22. Erijman, A., Aizner, Y. and Shifman, J. M. (2011). Multispecific recognition: mechanism, evolution and design. Biochemistry 50, 602-611. https://doi.org/10.1021/bi101563v
  23. Zhu, H., Bilgin, M., Bangham, R., Hall, D., Casamayor, A., Bertone, P., Lan, N., Jansen, R., Bidlingmaier, S., Houfek, T., Mitchell, T., Miller, P., Dean, R. A., Gerstein, M. and Snyder, M. (2001). Global analysis of protein activities using proteome chips. Science 293, 2101-2105. https://doi.org/10.1126/science.1062191
  24. Gelperin, D. M., White, M. A., Wilkinson, M. L., Kon, Y., Kung, L. A., Wise, K. J., Lopez-Hoyo, N., Jiang, L., Piccirillo, S., Yu, H., Gerstein, M., Dumont, M. E., Phizicky, E. M., Snyder, M. and Grayhack, E. J. (2005). Biochemical and genetic analysis of yeast proteome with moveabls ORF collection. Genes & Development 19, 2816-2826. https://doi.org/10.1101/gad.1362105
  25. Malys, N., Wishart, J. A., Oliver, S. G. and McCarthy, J. E. G. (2011). Protein production in S. cerevisiae for systems biology studies. Methods Enzymol. 500, 197-212. https://doi.org/10.1016/B978-0-12-385118-5.00011-6
  26. Alexander, R. R., Griffiths, J. M. and Wilkinson, M. L. (1985). Basic Biochemical Methods. pp. 241. John Wiley & Sons Inc., New York, U.S.A.
  27. Cheng, Y. and Prusoff, W. H. (1973). Relationship between inhibition constant (Ki) and the concentration of inhibitor which causes 50% inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099-3108. https://doi.org/10.1016/0006-2952(73)90196-2
  28. Ghaemmaghami, S., Huh, W. K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K. and Weissman, J. S. (2003). Global analysis of protein expression in yeast. Nature 425, 737-741. https://doi.org/10.1038/nature02046
  29. Jorgensen, P., Nishikawa, J. L., Breitkreutz, B. J. and Tyers, M. (2002). Systematic identification of pathways that couple cell growth and division in yeast. Science 297, 395-400. https://doi.org/10.1126/science.1070850
  30. Hucka, M., Finney, A., Sauro, H. M., Bolouri, H., Doyle, J. C., Kitano, H., Arkin, A. P., Bornstein, B. J., Bray, D., Cornish-Bowden, A., Cuellar, A. A., Dronov, S., Gilles, E. D., Ginkel, M., Gor, V., Goryanin, I. I., Hedley, W. J., Hodgman, T. C., Hofmeyr, J. H., Hunter, P. J., Juty, N. S., Kasberger, J. L., Kremling, A., Kummer, U., Le Novère, N., Loew, L. M., Lucio, D., Mendes, P., Minch, E., Mjolsness, E. D., Nakayama, Y., Nelson, M. R., Nielsen, P. F., Sakurada, T., Schaff, J. C., Shapiro, B. E., Shimizu, T. S., Spence, H. D., Stelling, J., Takahashi, K., Tomita, M., Wagner, J., Wang, J. and SBML Forum. (2003). The Systems Biology Markup Language (SBML): A medium for representation and exchange of biochemical network models. Bioinformatics 19, 524-531. https://doi.org/10.1093/bioinformatics/btg015
  31. Hoops, S., Sahle, S., Gauges, R., Lee, C., Pahle, J., Simus, N., Singhal, M., Xu, L., Mendes, P. and Kummer, U. (2006). COPASI-a COmplex PAthway SImulator. Bioinformatics 22, 3067-3074. https://doi.org/10.1093/bioinformatics/btl485

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