Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Wolfgang Knecht, N.E. Mikkelsen, A.R. Clausen, M. Willer, H. Eklund, Z. Gojkovic, Jure Piskur

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) can additionally sensitize human cancer cell lines towards the anti-cancer drug gemcitabine. We show that this property is based on the Dm-dNK ability to efficiently phosphorylate gemcitabine. The 2.2 angstrom resolution structure of DmdNK in complex with gemcitabine shows that the residues Tyr70 and Arg105 play a crucial role in the firm positioning of gemcitabine by extra interactions made by the fluoride atoms. This explains why gemcitabine is a good substrate for Dm-dNK(.
    Original languageEnglish
    JournalBiochemical and Biophysical Research Communications
    Volume382
    Issue number2
    Pages (from-to)430-433
    ISSN0006-291X
    DOIs
    Publication statusPublished - 2009

    Keywords

    • Structure-function relationship
    • Deoxyribonucleoside kinase
    • Salvage pathway
    • Gene-therapy
    • Cancer
    • Nucleoside analogs

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