Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Nils Mikkelsen; Hans Eklund

doi:10.1016/j.bbrc.2009.03.041

Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Nils Mikkelsen
, Hans Eklund

Publication: Contribution to journal › Journal article › peer-review

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.

Original language	English
Pages (from-to)	430-433
Number of pages	4
Journal	Biochemical and Biophysical Research Communications
Volume	382
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2009.03.041
Publication status	Published - 2009

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

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10.1016/j.bbrc.2009.03.041

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title = "Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine",

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

author = "Nils Mikkelsen and Hans Eklund",

year = "2009",

doi = "10.1016/j.bbrc.2009.03.041",

language = "English",

volume = "382",

pages = "430--433",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier B.V.",

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}

TY - JOUR

T1 - Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

AU - Mikkelsen, Nils

AU - Eklund, Hans

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Nucleoside analogs

KW - Deoxyribonucleoside kinase

KW - Gene-therapy

KW - Cancer

KW - Salvage pathway

KW - Structure-function relationship

KW - Nucleoside analogs

KW - Deoxyribonucleoside kinase

KW - Gene-therapy

KW - Cancer

KW - Salvage pathway

KW - Structure-function relationship

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

U2 - 10.1016/j.bbrc.2009.03.041

DO - 10.1016/j.bbrc.2009.03.041

M3 - Journal article

C2 - 19285960

SN - 0006-291X

VL - 382

SP - 430

EP - 433

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

Abstract

UN SDGs

Keywords

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