Bencharit_2003_Nat.Struct.Biol_10_349

Reference

Title : Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme - Bencharit_2003_Nat.Struct.Biol_10_349
Author(s) : Bencharit S , Morton CL , Xue Y , Potter PM , Redinbo MR
Ref : Nat Struct Biol , 10 :349 , 2003
Abstract :

We present the first crystal structures of a human protein bound to analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and cocaine, and the detoxification of organophosphate chemical weapons, such as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide explicit details about narcotic metabolism in humans. The hCE1 active site contains both specific and promiscuous compartments, which enable the enzyme to act on structurally distinct chemicals. A selective surface ligand-binding site regulates the trimer-hexamer equilibrium of hCE1 and allows each hCE1 monomer to bind two narcotic molecules simultaneously. The bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure.

PubMedSearch : Bencharit_2003_Nat.Struct.Biol_10_349
PubMedID: 12679808
Gene_locus related to this paper: human-CES1

Related information

Substrate Homatropine    N-Methylnaloxonium
Gene_locus Homatropine    N-Methylnaloxonium    human-CES1
Structure Homatropine    N-Methylnaloxonium    human-CES1    1MX5    1MX9

Citations formats

Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR (2003)
Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme
Nat Struct Biol 10 :349

Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR (2003)
Nat Struct Biol 10 :349