Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine.

نویسندگان

  • Wolfgang Knecht
  • Nils Egil Mikkelsen
  • Anders Ranegaard Clausen
  • Mette Willer
  • Hans Eklund
  • Zoran Gojković
  • Jure Piskur
چکیده

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 2.2A resolution structure of Dm-dNK 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.

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عنوان ژورنال:
  • Biochemical and biophysical research communications

دوره 382 2  شماره 

صفحات  -

تاریخ انتشار 2009