Mosquito has a single multisubstrate deoxyribonucleoside kinase characterized by unique substrate specificity

Wolfgang Knecht, G.E. Petersen, Michael Sandrini, L. Søndergaard, B. Munch-Petersen, Jure Piskur

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    In mammals four deoxyribonucleoside kinases, with a relatively restricted specificity, catalyze the phosphorylation of the four natural deoxyribonucleosides. When cultured mosquito cells, originating from the malaria vector Anopheles gambiae, were examined for deoxyribonucleoside kinase activities, only a single enzyme was isolated. Subsequently, the corresponding gene was cloned and over-expressed. While the mosquito kinase (Ag-dNK) phosphorylated all four natural deoxyribonucleosides, it displayed an unexpectedly higher relative efficiency for the phosphorylation of purine versus pyrimidine deoxyribonucleosides than the fruit fly multisubstrate deoxyribonucleoside kinase (EC 2.7.1.145). In addition, Ag-dNK could also phosphorylate some medically interesting nucleoside analogs, like stavudine (D4T), 2-chloro-deoxyadenosine (CdA) and 5-bromo-vinyl-deoxyuridine (BVDU). Although the biological significance of multisubstrate deoxyribonucleoside kinases and their diversity among insects remains unclear, the observed variation provides a whole range of applications, as species specific and highly selective targets for insecticides, they have a potential to be used in the enzymatic production of various (di-)(deoxy-)ribonucleoside monophosphates, and as suicide genes in gene therapy.
    Original languageEnglish
    JournalNucleic Acids Research
    Volume31
    Issue number6
    Pages (from-to)1665-1672
    ISSN0305-1048
    DOIs
    Publication statusPublished - 2003

    Fingerprint Dive into the research topics of 'Mosquito has a single multisubstrate deoxyribonucleoside kinase characterized by unique substrate specificity'. Together they form a unique fingerprint.

    Cite this