Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

作者：Knecht Wolfgang; Mikkelsen Nils Egil; Clausen Anders Ranegaard; Willer Mette; Eklund Hans; Gojkovic Zoran; Piskur Jure^*

来源：Biochemical and Biophysical Research Communications, 2009, 382(2): 430-433.

DOI：10.1016/j.bbrc.2009.03.041

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

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(.

• 出版日期2009-5-1