Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Journal Article · Fri May 01 00:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.03.041· OSTI ID:22199676

Knecht, Wolfgang ^[1]; Mikkelsen, Nils Egil ^[2]; Clausen, Anders Ranegaard ^[3]; Willer, Mette ^[4]; Eklund, Hans ^[2]; Gojkovic, Zoran ^[4]; Piskur, Jure ^[1]

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1. BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby (Denmark)
2. Department of Molecular Biology, Swedish University of Agricultural Sciences, Biomedical Centre, SE-751 24 Uppsala (Sweden)
3. Cell and Organism Biology, Lund University, Soelvegatan 35, SE-22362 Lund (Sweden)
4. ZGene A/S, Agern Alle 7, DK-2970 Horsholm (Denmark)

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 A 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.

• OSTI ID: 22199676
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 382, Issue 2; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
DROSOPHILA
DRUGS
FLUORIDES
GENE THERAPY
NEOPLASMS
STRUCTURE FUNCTIONS
SUBSTRATES