title: Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism.
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.
authors.affiliation: Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester, UK.
authors.forename: Oluwafemi
authors.initials: O
authors.lastname: Davies
authors.forename: Pedro
authors.initials: P
authors.lastname: Mendes
authors.forename: Kieran
authors.initials: K
authors.lastname: Smallbone
authors.forename: Naglis
authors.initials: N
authors.lastname: Malys
mesh_terms: D003198:Computer Simulation; D003641:Deamination; D007700:Kinetics; D008958:Models, Molecular; D011685:Purine Nucleotides / Q000737:chemistry* / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D000097630:Inosine Triphosphatase
chemical_list: D011685:Purine Nucleotides; D011755:Pyrophosphatases; D029701:Saccharomyces cerevisiae Proteins; D000097630:Inosine Triphosphatase; C117841:HAM1 protein, S cerevisiae