9KWL

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

This is a non-PDB format compatible entry.

Summary for 9KWL

• Entry DOI: 10.2210/pdb9kwl/pdb
• Descriptor: Liver carboxylesterase 1, (1R)-1-(3,4-dichlorophenyl)-2,2,2-tris(fluoranyl)ethanol, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: hces1a, covalent, inhibitors, sbdd, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 59069.68

Authors

Gai, C.,Zhao, Q. (deposition date: 2024-12-06, release date: 2025-01-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.83 Å)