1LWX

AZT DIPHOSPHATE BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE

1LWX の概要

• エントリーDOI: 10.2210/pdb1lwx/pdb
• 分子名称: NUCLEOSIDE DIPHOSPHATE KINASE, MAGNESIUM ION, 3'-AZIDO-3'-DEOXYTHYMIDINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: phosphotransferase, antiviral agent, azidothymidine
• 由来する生物種: Dictyostelium discoideum
• 細胞内の位置: Cytoplasm: P22887
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 51650.15

構造登録者

Janin, J.,Xu, Y. (登録日: 1997-04-30, 公開日: 1997-08-20, 最終更新日: 2024-02-14)

主引用文献

Xu, Y.,Sellam, O.,Morera, S.,Sarfati, S.,Biondi, R.,Veron, M.,Janin, J.
X-ray analysis of azido-thymidine diphosphate binding to nucleoside diphosphate kinase.
Proc.Natl.Acad.Sci.USA, 94:7162-7165, 1997

PubMed Abstract: To be effective as antiviral agent, AZT (3'-azido-3'-deoxythymidine) must be converted to a triphosphate derivative by cellular kinases. The conversion is inefficient and, to understand why AZT diphosphate is a poor substrate of nucleoside diphosphate (NDP) kinase, we determined a 2.3-A x-ray structure of a complex with the N119A point mutant of Dictyostelium NDP kinase. It shows that the analog binds at the same site and, except for the sugar ring pucker which is different, binds in the same way as the natural substrate thymidine diphosphate. However, the azido group that replaces the 3'OH of the deoxyribose in AZT displaces a lysine side chain involved in catalysis. Moreover, it is unable to make an internal hydrogen bond to the oxygen bridging the beta- and gamma-phosphate, which plays an important part in phosphate transfer.

PubMed: 9207061
DOI: 10.1073/pnas.94.14.7162

実験手法

X-RAY DIFFRACTION (2.3 Å)