Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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 [BMB reports 2012; 45(4): 259-264]
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 [BMB reports 2012; 45(4): 259-264]
참고문헌 (31)
- Sancar, A., "DNA repair enzymes", Ann. Rev. Biochem., 57, pp.29~67 (1988)
- Nguyen, T., "DNA damage and mutation in human cells exposed to nitric oxide in vitro", Proc. Nat. Acad. Sci. U.S.A., 89, pp.3030~3034 (1992)
- Nakabeppu, Y., "Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids", Biol. Chem., 387, pp.373~379 (2006)
- Nakabeppu, Y., "Oxidative damage in nucleic acids and Parkinson’s disease", J. Neurosci. Res., 85, pp.919~934 (2007)
- Rai, P., "Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence", Proc. Nat. Acad. Sci. U.S.A., 106, pp.169~174 (2009)
- Kong, Q., "Oxidative damage to RNA: mechanisms, consequences and diseases", Cell. Mol. Life Sci., 67, pp.1817~1829 (2010)
- Iyama, T., "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, pp.4834~4843 (2010)
- Sakumi, K., "ITPA protein, an enzyme that eliminates deaminated purine nucleoside triphosphates in cells", Mutation Res., 703, pp.43~50 (2010)
- Burgis, N. E., "Substrate specificity of RdgB protein, a deoxyribonucleoside triphosphate pyrophosphohydrolase", J. Biol. Chem., 282, pp.3531~3538 (2007)
- Savchenko, A., "Molecular basis of the antimutagenic activity of the house-cleaning inosine triphosphate pyrophosphatase RdgB from Escherichia coli", J. Mol. Biol., 374, pp.1091~1103 (2007)
- Noskov, V. N., "HAM 1, the gene controlling 6-N-hydroxylaminopurine sensitivity and mutagenesis in the yeast Saccharomyces cerevisiae", Yeast, 12, pp.17~29 (1996)
- Bochnert, B. R., "Complete analysis of cellular nucleotides by two-dimensional thin layer chromatography", J. Biol. Chem., 257, pp.9759~9769 (1982)
- Vanderheiden, B. S., "Human erythrocyte "ITPase": an ITP pyrophosphohydrolase", Biochim. Biophys. Acta, 215, pp.555~558 (1970)
- Rafty, L. A., "Analysis of O-acetyl-ADP-ribose as a target for Nudix ADP-ribose hydrolases", J. Biol. Chem., 277, pp.47114~47122 (2002)
- Gadsden, M. H., "dUTP pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae", EMBO J., 12, pp.4425~4431 (1993)
- Tchigvintsev, A., "Structure and activity of the Saccharomyces cerevisiae dUTP pyrophosphatase DUT1, an essential housekeeping enzyme", Biochem. J., 437, pp.243~253 (2011)
- Kennedy, E. J., "Pho5p and newly identified nucleotide pyrophosphatases", phosphodiesterases regulate extracellular nucleotide phosphate metabolism in Saccharomyces cerevisiae, 2005, pp.4, 1892~1901
- Malys N., "The ‘scavenger’ m7GpppX pyrophosphatase activity of Dcs1 modulates nutrient-induced responses in yeast", Nucleic Acids Res., 32, pp.3590~3600 (2004)
- Malys N., "Dcs2, a novel stress-induced modulator of m7GpppX pyrophosphatase activity that locates to P bodies", J. Mol. Biol., 363, pp.370~382 (2006)
- Keesey, J. K. Jr., "The product of the his4 gene cluster in Saccharomyces cerevisiae. A trifunctional polypeptide", J. Biol. Chem., 254, pp.7427~7433 (1979)
- Galperin, M. Y., "House cleaning, a part of good housekeeping", Mol. Microbiol., 59, pp.5~19 (2006)
- Erijman, A., "Multispecific recognition: mechanism, evolution and design", Biochemistry, 50, pp.602~611 (2011)
- Zhu, H., "Global analysis of protein activities using proteome chips", Science, 293, pp.2101~2105 (2001)
- Gelperin, D. M., "Biochemical and genetic analysis of yeast proteome with moveabls ORF collection", Genes & Development, 19, pp.2816~2826 (2005)
- Malys, N., "Protein production in S. cerevisiae for systems biology studies", Methods Enzymol., 500, pp.197~212 (2011)
- Alexander, R. R., "Basic Biochemical Methods", pp.241~ (1985), John Wiley& Sons Inc
- Cheng, Y., "Relationship between inhibition constant (Ki) and the concentration of in-hibitor which causes 50% inhibition (I50) of an enzymatic reaction", Biochem. Pharmacol., 22, pp.3099~3108 (1973)
- Ghaemmaghami, S., "Global analysis of protein expression in yeast", Nature, 425, pp.737~741 (2003)
- Jorgensen, P., "Systematic identification of pathways that couple cell growth and division in yeast", Science, 297, pp.395~400 (2002)
- Hucka, M., "The Systems Biology Markup Language (SBML): A medium for representation and exchange of biochemical network models", Bioinformatics, 19, pp.524~531 (2003)
- Hoops, S., "COPASI-a COmplex PAthway SImulator", Bioinformatics, 22, pp.3067~3074 (2006)