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Research article - Peer-reviewed, 2009

Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Mikkelsen, Nils; Eklund, Hans

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

Keywords

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

Published in

Biochemical and Biophysical Research Communications
2009, volume: 382, number: 2, pages: 430-433
Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE

Authors' information

Swedish University of Agricultural Sciences, Department of Molecular Biology
Eklund, Hans
Swedish University of Agricultural Sciences, Department of Molecular Biology

Sustainable Development Goals

SDG3 Good health and wellbeing

UKÄ Subject classification

Biochemistry and Molecular Biology
Biophysics

Publication Identifiers

DOI: https://doi.org/10.1016/j.bbrc.2009.03.041

URI (permanent link to this page)

https://res.slu.se/id/publ/44592