Knecht, W., Mikkelsen, N.E., Clausen, A.R., Willer, M., Eklund, H., Gojković, Z., Piskur, J. (2009). Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine. Biochem. Biophys. Res. Commun. 382(2): 430--433.
FlyBase ID
FBrf0207706
Publication Type
Research paper
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 2.2A 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.
