5FIU

Binding and structural studies of a 5,5-difluoromethyl adenosine nucleoside with the fluorinase enzyme

5FIU の概要

• エントリーDOI: 10.2210/pdb5fiu/pdb
• 分子名称: 5'-FLUORO-5'-DEOXY-ADENOSINE SYNTHASE, 5,5-DIFLUOROMETHYL ADENOSINE, L(+)-TARTARIC ACID, ... (4 entities in total)
• 機能のキーワード: transferase, fluorinase, difluoromethyl, isothermal titration calorimetry
• 由来する生物種: STREPTOMYCES CATTLEYA
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 98516.40

構造登録者

Thompson, S.,McMahon, S.A.,Naismith, J.H.,O'Hagan, D. (登録日: 2015-10-02, 公開日: 2015-12-23, 最終更新日: 2024-01-10)

主引用文献

Thompson, S.,Mcmahon, S.A.,Naismith, J.H.,O'Hagan, D.
Exploration of a Potential Difluoromethyl-Nucleoside Substrate with the Fluorinase Enzyme.
Bioorg.Chem., 64:37-, 2015

PubMed Abstract: The investigation of a difluoromethyl-bearing nucleoside with the fluorinase enzyme is described. 5',5'-Difluoro-5'-deoxyadenosine 7 (F2DA) was synthesised from adenosine, and found to bind to the fluorinase enzyme by isothermal titration calorimetry with similar affinity compared to 5'-fluoro-5'-deoxyadenosine 2 (FDA), the natural product of the enzymatic reaction. F2DA7 was found, however, not to undergo the enzyme catalysed reaction with L-selenomethionine, unlike FDA 2, which undergoes reaction with L-selenomethionine to generate Se-adenosylselenomethionine. A co-crystal structure of the fluorinase and F2DA7 and tartrate was solved to 1.8Å, and revealed that the difluoromethyl group bridges interactions known to be essential for activation of the single fluorine in FDA 2. An unusual hydrogen bonding interaction between the hydrogen of the difluoromethyl group and one of the hydroxyl oxygens of the tartrate ligand was also observed. The bridging interactions, coupled with the inherently stronger C-F bond in the difluoromethyl group, offers an explanation for why no reaction is observed.

PubMed: 26642178
DOI: 10.1016/J.BIOORG.2015.11.003

実験手法

X-RAY DIFFRACTION (1.84 Å)