Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Summary, in English

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(. (C) 2009 Elsevier Inc. All rights reserved.

• Författare: Wolfgang Knecht; Nils Egil Mikkelsen; Anders Ranegaard Clausen; Mette Willer; Hans Eklund; Zoran Gojkovic; Jure Piskur
• Avdelning/ar: Biologiska institutionen; Molekylär cellbiologi
• Publiceringsår: 2009
• Språk: Engelska
• Sidor: 430-433
• Publikation/Tidskrift/Serie: Biochemical and Biophysical Research Communications
• Volym: 382
• Issue: 2
• Länkar: http://dx.doi.org/10.1016/j.bbrc.2009.03.041
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Biological Sciences
• Nyckelord: Structure-function relationship; Salvage pathway; Cancer; Gene-therapy; Nucleoside analogs; Deoxyribonucleoside kinase
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1090-2104