Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Sammanfattning

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.

Nyckelord

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

Publicerad i

Biochemical and Biophysical Research Communications
2009, volym: 382, nummer: 2, sidor: 430-433
Utgivare: ACADEMIC PRESS INC ELSEVIER SCIENCE

SLU författare

• Mikkelsen, Nils

  • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
    

• Eklund, Hans

  • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
    

Globala målen (SDG)

SDG3 God hälsa och välbefinnande

UKÄ forskningsämne

Biokemi och molekylärbiologi
Biofysik

Publikationens identifierare

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

Permanent länk till denna sida (URI)

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