Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Research output: Contribution to journalArticle

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.

Details

Authors
  • Wolfgang Knecht
  • Nils Egil Mikkelsen
  • Anders Ranegaard Clausen
  • Mette Willer
  • Hans Eklund
  • Zoran Gojkovic
  • Jure Piskur
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences

Keywords

  • Structure-function relationship, Salvage pathway, Cancer, Gene-therapy, Nucleoside analogs, Deoxyribonucleoside kinase
Original languageEnglish
Pages (from-to)430-433
JournalBiochemical and Biophysical Research Communications
Volume382
Issue number2
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes