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Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Knecht, Wolfgang; Mikkelsen, Nils Egil; Clausen, Anders Ranegaard LU ; Willer, Mette; Eklund, Hans; Gojkovic, Zoran and Piskur, Jure LU (2009) In Biochemical and Biophysical Research Communications 382(2). p.430-433
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.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Structure-function relationship, Salvage pathway, Cancer, Gene-therapy, Nucleoside analogs, Deoxyribonucleoside kinase
in
Biochemical and Biophysical Research Communications
volume
382
issue
2
pages
430 - 433
publisher
Elsevier
external identifiers
  • wos:000265279300039
  • scopus:63349095879
ISSN
1090-2104
DOI
10.1016/j.bbrc.2009.03.041
language
English
LU publication?
yes
id
bf59b6d7-c510-41e2-9613-dee11d62665f (old id 1400387)
date added to LUP
2009-06-15 14:13:46
date last changed
2017-04-09 03:54:48
@article{bf59b6d7-c510-41e2-9613-dee11d62665f,
  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.},
  author       = {Knecht, Wolfgang and Mikkelsen, Nils Egil and Clausen, Anders Ranegaard and Willer, Mette and Eklund, Hans and Gojkovic, Zoran and Piskur, Jure},
  issn         = {1090-2104},
  keyword      = {Structure-function relationship,Salvage pathway,Cancer,Gene-therapy,Nucleoside analogs,Deoxyribonucleoside kinase},
  language     = {eng},
  number       = {2},
  pages        = {430--433},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2009.03.041},
  volume       = {382},
  year         = {2009},
}