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

Publikation: Bidrag till tidskrift › Artikel i vetenskaplig tidskrift › Peer review

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.

Originalspråk	Engelska
Sidor (från-till)	430-433
Antal sidor	4
Tidskrift	Biochemical and Biophysical Research Communications
Volym	382
Nummer	2
DOI	https://doi.org/10.1016/j.bbrc.2009.03.041
Status	Publicerad - 2009

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Nyckelord

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",

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

language = "English",

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T1 - Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

AU - Mikkelsen, Nils

AU - Eklund, Hans

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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

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DO - 10.1016/j.bbrc.2009.03.041

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JO - Biochemical and Biophysical Research Communications

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