5AV2

Crystal structure of DAPK1-kaempferol complex in the presence of bromide ions.

5AV2 の概要

• エントリーDOI: 10.2210/pdb5av2/pdb
• 関連するPDBエントリー: 5AUT 5AUU 5AUV 5AUW 5AUX 5AUY 5AUZ 5AV0 5AV1 5AV3 5AV4
• 分子名称: Death-associated protein kinase 1, 3,5,7-TRIHYDROXY-2-(4-HYDROXYPHENYL)-4H-CHROMEN-4-ONE, BROMIDE ION, ... (4 entities in total)
• 機能のキーワード: death-associated protein kinase 1, serine/threonine protein kinase, natural flavonoid, 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: 34641.97

構造登録者

Yokoyama, T.,Mizuguchi, M. (登録日: 2015-06-10, 公開日: 2015-10-07, 最終更新日: 2024-03-20)

主引用文献

Yokoyama, T.,Kosaka, Y.,Mizuguchi, M.
Structural Insight into the Interactions between Death-Associated Protein Kinase 1 and Natural Flavonoids.
J.Med.Chem., 58:7400-7408, 2015

PubMed Abstract: Death-associated protein kinase 1 (DAPK1) is a 160 kDa serine/threonine protein kinase that belongs to the Ca(2+)/calmodulin-dependent protein kinase subfamily. DAPK1 is a possible target for the treatment of acute ischemic stroke and endometrial adenocarcinomas. In the present study, we investigated the binding characteristics of 17 natural flavonoids to DAPK1 using a 1-anilinonaphthalene-8-sulfonic acid competitive binding assay and revealed that morin was the strongest binder among the selected compounds. The crystallographic analysis of DAPK1 and 7 selected flavonoid complexes revealed the structure-binding affinity relationship in atomic-level detail. It was suggested that the high affinity of morin could be accounted for by the ionic interaction between 2'-OH and K42 and that such an interaction would not take place with either cyclin-dependent protein kinases or PIM kinases because of their broader entrance regions. Thus, morin would be a more selective inhibitor of DAPK1 than either of these other types of kinases. In addition, we found that the binding of kaempferol to DAPK1 was associated with a chloride ion. The present study provides a better understanding of the molecular properties of the ATP site of DAPK1 and may be useful for the design of specific DAPK1 inhibitors.

PubMed: 26322379
DOI: 10.1021/acs.jmedchem.5b00893

実験手法

X-RAY DIFFRACTION (1.502 Å)