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Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Författare:
  • Wolfgang Knecht
  • Nils Egil Mikkelsen
  • Anders Ranegaard Clausen
  • Mette Willer
  • Hans Eklund
  • Zoran Gojkovic
  • Jure Piskur (Professor)
Publiceringsår: 2009
Språk: Engelska
Sidor: 430-433
Publikation/Tidskrift/Serie: Biochemical And Biophysical Research Communications
Volym: 382
Nummer: 2
Dokumenttyp: Artikel
Förlag: Academic Press Inc Elsevier Science

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.

Disputation

Nyckelord

  • Medicine and Health Sciences
  • Structure-function relationship
  • Salvage pathway
  • Cancer
  • Gene-therapy
  • Nucleoside analogs
  • Deoxyribonucleoside kinase

Övriga

Published
Yes
  • ISSN: 0006-291X

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