2VQS

Structural Studies of Nucleoside Analog and Feedback Inhibitor Binding to Drosophila Melanogaster Multisubstrate Deoxyribonucleoside Kinase

2VQS の概要

• エントリーDOI: 10.2210/pdb2vqs/pdb
• 関連するPDBエントリー: 1J90 1OE0 1OT3 1ZM7 1ZMX 2JCS 2VP0 2VP2 2VP4 2VP5 2VP6 2VP9 2VPP
• 分子名称: DEOXYNUCLEOSIDE KINASE, SULFATE ION, 5-BROMOVINYLDEOXYURIDINE, ... (4 entities in total)
• 機能のキーワード: atp-binding, dna synthesis, phosphoprotein, feedback inhibition, deoxyribonucleoside kinase, salvage pathway, nucleotide-binding, dttp, kinase, complex, drosophila, transferase
• 由来する生物種: DROSOPHILA MELANOGASTER (FRUIT FLY)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 109343.62

構造登録者

Mikkelsen, N.E.,Munch-Petersen, B.,Eklund, H. (登録日: 2008-03-18, 公開日: 2008-04-29, 最終更新日: 2023-12-13)

主引用文献

Mikkelsen, N.E.,Munch-Petersen, B.,Eklund, H.
Structural Studies of Nucleoside Analog and Feedback Inhibitor Binding to Drosophila Melanogaster Multisubstrate Deoxyribonucleoside Kinase.
FEBS J., 275:2151-, 2008

PubMed Abstract: The Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (dNK; EC 2.7.1.145) has a high turnover rate and a wide substrate range that makes it a very good candidate for gene therapy. This concept is based on introducing a suicide gene into malignant cells in order to activate a prodrug that eventually may kill the cell. To be able to optimize the function of dNK, it is vital to have structural information of dNK complexes. In this study we present crystal structures of dNK complexed with four different nucleoside analogs (floxuridine, brivudine, zidovudine and zalcitabine) and relate them to the binding of substrate and feedback inhibitors. dCTP and dGTP bind with the base in the substrate site, similarly to the binding of the feedback inhibitor dTTP. All nucleoside analogs investigated bound in a manner similar to that of the pyrimidine substrates, with many interactions in common. In contrast, the base of dGTP adopted a syn-conformation to adapt to the available space of the active site.

PubMed: 18384378
DOI: 10.1111/J.1742-4658.2008.06369.X

実験手法

X-RAY DIFFRACTION (2.9 Å)