9KWL

hCES1A contently binding with compound F-3 at the catalytic pocket.

これはPDB形式変換不可エントリーです。

9KWL の概要

• エントリーDOI: 10.2210/pdb9kwl/pdb
• 分子名称: Liver carboxylesterase 1, (1R)-1-(3,4-dichlorophenyl)-2,2,2-tris(fluoranyl)ethanol, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: hces1a, covalent, inhibitors, sbdd, hydrolase
• 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: 59069.68

構造登録者

Gai, C.,Zhao, Q. (登録日: 2024-12-06, 公開日: 2025-01-29)

主引用文献

Gai, C.,Zhang, Y.,Zhang, S.,Hu, X.,Song, Y.Q.,Zhuang, X.,Chai, X.,Zou, Y.,Ge, G.B.,Zhao, Q.
The study of halogen effect on the reactivity of the serine-targeting covalent warheads.
Front Chem, 12:1504453-1504453, 2024

PubMed Abstract: Halogens favorably contributes to the drug potency and metabolic stability via electrostatic interactions. Herein, the halogen effects on the reactivity of the halogenated 2,2,2-trifluoroacetophenones as serine-targeting covalent warheads were investigated. Our results showed that introducing halogen atoms, especially Cl or Br, into the phenyl scaffold would influence the electron density around the ring, which led to different time-dependent inhibition response to the target serine hydrolase (hCES1A). Co-crystallography analysis not only verified that halogenated molecules preferred to form covalent adducts, but also provided the conformational information for the design of covalent inhibitors targeting to hCES1A protein for the treatment of drug-induced acute enteritis.

PubMed: 39691824
DOI: 10.3389/fchem.2024.1504453

実験手法

X-RAY DIFFRACTION (1.83 Å)