Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Wolfgang Knecht, Nils Egil Mikkelsen, Anders Ranegaard Clausen, Mette Willer, Hans Eklund, Zoran Gojkovic, Jure Piskur

Research output: Contribution to journalArticlepeer-review

13 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)430-433
JournalBiochemical and Biophysical Research Communications
Volume382
Issue number2
DOIs
Publication statusPublished - 2009

Subject classification (UKÄ)

  • Biological Sciences

Keywords

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

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