We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

9kwl

From Proteopedia

Jump to: navigation, search

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

Structural highlights

9kwl is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.83Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EST1_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 PubMed

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.

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

↑ Brzezinski MR, Abraham TL, Stone CL, Dean RA, Bosron WF. Purification and characterization of a human liver cocaine carboxylesterase that catalyzes the production of benzoylecgonine and the formation of cocaethylene from alcohol and cocaine. Biochem Pharmacol. 1994 Nov 1;48(9):1747-55. PMID:7980644
↑ Pindel EV, Kedishvili NY, Abraham TL, Brzezinski MR, Zhang J, Dean RA, Bosron WF. Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin. J Biol Chem. 1997 Jun 6;272(23):14769-75. PMID:9169443
↑ Gai C, Zhang Y, Zhang S, Hu X, Song YQ, Zhuang X, Chai X, Zou Y, Ge GB, Zhao Q. The study of halogen effect on the reactivity of the serine-targeting covalent warheads. Front Chem. 2024 Dec 3;12:1504453. PMID:39691824 doi:10.3389/fchem.2024.1504453