3WKE

Crystal structure of soluble epoxide hydrolase in complex with t-AUCB

3WKE の概要

• エントリーDOI: 10.2210/pdb3wke/pdb
• 関連するPDBエントリー: 3KWD 3WK4 3WK5 3WK6 3WK7 3WK8 3WK9 3WKA 3WKB 3WKC
• 分子名称: Bifunctional epoxide hydrolase 2, MAGNESIUM ION, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P34913
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64046.31

構造登録者

Amano, Y.,Yamaguchi, T.,Tanabe, E. (登録日: 2013-10-18, 公開日: 2014-04-16, 最終更新日: 2024-05-29)

主引用文献

Amano, Y.,Yamaguchi, T.,Tanabe, E.
Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.
Bioorg.Med.Chem., 22:2427-2434, 2014

PubMed Abstract: Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH.

PubMed: 24656800
DOI: 10.1016/j.bmc.2014.03.001

実験手法

X-RAY DIFFRACTION (2.75 Å)