Title : Human carboxylesterase 1: from drug metabolism to drug discovery - Redinbo_2003_Biochem.Soc.Trans_31_620
Author(s) : Redinbo MR , Bencharit S , Potter PM
Ref : Biochemical Society Transactions , 31 :620 , 2003
Abstract :

Human carboxylesterase 1 (hCE1) is a serine esterase involved in both drug metabolism and activation, as well as other biological processes. hCE1 catalyses the hydrolysis of heroin and cocaine, and the transesterification of cocaine in the presence of ethanol to the toxic metabolite cocaethylene. We have determined the crystal structures of hCE1 in complex with either the cocaine analogue homatropine or the heroin analogue naloxone. These are the first structures of a human carboxylesterase, and they provide details about narcotic metabolism in humans. hCE1's active site contains rigid and flexible pockets, explaining the enzyme's ability to act both specifically and promiscuously. hCE1 has also been reported to contain cholesteryl ester hydrolase, fatty acyl-CoA hydrolase and acyl-CoA:cholesterol acyltransferase activities, and thus appears to be involved in cholesterol metabolism. Since the enzyme may be useful as a treatment for cocaine overdose, and may afford protection against chemical weapons like Sarin, Soman and VX gas, hCE1 could serve as both a drug and a drug target. Selective hCE1 inhibitors targeted to several sites on the enzyme may also pave the way for novel clinical tools to manage cholesterol homoeostasis in humans.

PubMedSearch : Redinbo_2003_Biochem.Soc.Trans_31_620
PubMedID: 12773168
Gene_locus related to this paper: human-CES1

Related information

Gene_locus human-CES1

Citations formats

Redinbo MR, Bencharit S, Potter PM (2003)
Human carboxylesterase 1: from drug metabolism to drug discovery
Biochemical Society Transactions 31 :620

Redinbo MR, Bencharit S, Potter PM (2003)
Biochemical Society Transactions 31 :620