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Research article - Peer-reviewed, 2009

Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Mikkelsen, Nils; Eklund, Hans

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(. (C) 2009 Elsevier Inc. All rights reserved.

Keywords

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

Published in

Biochemical and Biophysical Research Communications
2009, Volume: 382, number: 2, pages: 430-433
Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE

      SLU Authors

    • Mikkelsen, Nils

      • Department of Molecular Biology, Swedish University of Agricultural Sciences
      • Eklund, Hans

        • Department of Molecular Biology, Swedish University of Agricultural Sciences

      Sustainable Development Goals

      SDG3 Good health and well-being

      UKÄ Subject classification

      Biochemistry and Molecular Biology
      Biophysics

      Publication identifier

      DOI: https://doi.org/10.1016/j.bbrc.2009.03.041

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/44592