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(.
Original language | English |
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Journal | Biochemical and Biophysical Research Communications |
Volume | 382 |
Issue number | 2 |
Pages (from-to) | 430-433 |
ISSN | 0006-291X |
DOIs | |
Publication status | Published - 2009 |
Keywords
- Structure-function relationship
- Deoxyribonucleoside kinase
- Salvage pathway
- Gene-therapy
- Cancer
- Nucleoside analogs