Kinetic properties and inhibition of the dimeric dUTPase-dUDPase from Campylobacter jejuni

J.A. Musso-Buendía, A.E. Vidal, J. Carrero-Lérida, L.M. Ruiz-Pérez, D. González-Pacanowska, G. Kasinthan, C. Nguyen, I.H. Gilbert, N.G. Johansson, Keith Wilson

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    5 Citations (Scopus)

    Abstract

    The enzyme deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) catalyses the hydrolysis of dUTP to dUMP and PPi thus controlling the incorporation of uracil into DNA genomes. In Campylobacter jejuni dUTPase exhibits structural properties of dimeric proteins characteristic of protozoa of the Kinetoplastidae family. In the present study we perform a kinetic analysis of Campylobacter dUTPase using the continuous spectrophotometric method and show that the enzyme is highly specific for deoxyuridine nucleotides. The Michaelis-Menten constant for dUTP was 0.66 µM while the k was 12.3 s. dUDP was also efficiently hydrolysed although the specificity constant, k/K, was five fold lower than for dUTP. The reaction product and the non hydrolysable analogue a,ß imido dUDP are potent inhibitors of the enzyme while several analogues of dUMP with substituents at the 3'- and 5'-positions active against trimeric dUTPases, show poor inhibitory activity. Apparent structural and kinetic differences with other eukaryotic dUTPases suggest that the present enzyme might be exploited as a target for new drugs against campylobacteriosis.
    Original languageEnglish
    Pages (from-to)111-116
    Number of pages6
    JournalJournal of Enzyme Inhibition and Medicinal Chemistry
    Volume24
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2009

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  • Cite this

    Musso-Buendía, J. A., Vidal, A. E., Carrero-Lérida, J., Ruiz-Pérez, L. M., González-Pacanowska, D., Kasinthan, G., Nguyen, C., Gilbert, I. H., Johansson, N. G., & Wilson, K. (2009). Kinetic properties and inhibition of the dimeric dUTPase-dUDPase from Campylobacter jejuni. Journal of Enzyme Inhibition and Medicinal Chemistry, 24(1), 111-116. https://doi.org/10.1080/14756360801915476