黑腹果蝇脱氧核糖核苷激酶激活吉西他滨。

Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine.

作者信息

Knecht Wolfgang, Mikkelsen Nils Egil, Clausen Anders Ranegaard, Willer Mette, Eklund Hans, Gojković Zoran, Piskur Jure

机构信息

BioCentrum-DTU, Technical University of Denmark, Lyngby, Denmark.

出版信息

Biochem Biophys Res Commun. 2009 May 1;382(2):430-3. doi: 10.1016/j.bbrc.2009.03.041. Epub 2009 Mar 13.

DOI:10.1016/j.bbrc.2009.03.041

PMID:19285960

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 2.2A resolution structure of Dm-dNK 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.

摘要

果蝇多底物脱氧核糖核苷激酶（Dm-dNK）还能使人类癌细胞系对抗癌药物吉西他滨更敏感。我们发现这种特性基于Dm-dNK高效磷酸化吉西他滨的能力。Dm-dNK与吉西他滨复合物的2.2埃分辨率结构表明，酪氨酸70（Tyr70）和精氨酸105（Arg105）残基通过氟原子产生的额外相互作用在吉西他滨的稳固定位中起关键作用。这解释了为什么吉西他滨是Dm-dNK的良好底物。