9kwl
From Proteopedia
hCES1A contently binding with compound F-3 at the catalytic pocket.
Structural highlights
FunctionEST1_HUMAN Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.[1] [2] Publication Abstract from PubMedHalogens 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. The study of halogen effect on the reactivity of the serine-targeting covalent warheads.,Gai C, Zhang Y, Zhang S, Hu X, Song YQ, Zhuang X, Chai X, Zou Y, Ge GB, Zhao Q Front Chem. 2024 Dec 3;12:1504453. doi: 10.3389/fchem.2024.1504453. eCollection , 2024. PMID:39691824[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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