Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

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