Journal article
Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine
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(.
| Language: | English |
|---|---|
| Year: | 2009 |
| Pages: | 430-433 |
| ISSN: | 10902104 and 0006291x |
| Types: | Journal article |
| DOI: | 10.1016/j.bbrc.2009.03.041 |
Cancer Deoxyribonucleoside kinase Gene-therapy Nucleoside analogs SDG 3 - Good Health and Well-being Salvage pathway Structure-function relationship
Animals Antimetabolites, Antineoplastic Cell Line, Tumor Deoxycytidine Drosophila melanogaster Drug Resistance, Neoplasm Gemcitabine Humans Phosphotransferases (Alcohol Group Acceptor) Protein Conformation Structure-Activity Relationship Structure–function relationship Substrate Specificity deoxyribonucleoside kinases
