8IE6

Crystal structure of DAPK1 in complex with pinostilbene

8IE6 の概要

• エントリーDOI: 10.2210/pdb8ie6/pdb
• 分子名称: Death-associated protein kinase 1, 3-[(E)-2-(4-hydroxyphenyl)ethenyl]-5-methoxy-phenol, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: inhibitor, complex, protein kinase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34230.80

構造登録者

Yokoyama, T. (登録日: 2023-02-15, 公開日: 2023-05-24, 最終更新日: 2023-10-04)

主引用文献

Yokoyama, T.,Kusaka, K.
Characterization of the molecular interactions between resveratrol derivatives and death-associated protein kinase 1.
Febs J., 290:4465-4479, 2023

PubMed Abstract: Death-associated protein kinase 1 (DAPK1), a Ca2+/calmodulin-regulated serine/threonine kinase, regulates cell apoptosis and autophagy and has been implicated in the pathogenesis of Alzheimer's disease (AD). Targeting DAPK1 may be a promising approach for treating AD. In our previous study, we found that a natural polyphenol, resveratrol (1), is a moderate DAPK1 inhibitor. In the present study, we investigated the interactions between natural and synthetic derivatives of 1 and DAPK1. Binding assays including intrinsic fluorescence quenching, protein thermal shift and isothermal titration calorimetry indicated that oxyresveratrol (3), a hydroxylated derivative, and pinostilbene (5), a methoxylated derivative, bind to DAPK1 with comparable affinity to 1. The enzymatic assay showed that 3 more effectively inhibits the intrinsic ATPase activity of DAPK1 compared with 1. Crystallographic analysis revealed that the binding modes of the methoxylated derivatives were different from those of 1 and 3, resulting in a unique interaction. Our results suggest that 3 may be helpful in treating AD and provide a clue for the development of promising DAPK1 inhibitors.

PubMed: 37171222
DOI: 10.1111/febs.16817

実験手法

X-RAY DIFFRACTION (1.701 Å)