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Literature summary extracted from

  • Bencharit, S.; Morton, C.L.; Xue, Y.; Potter, P.M.; Redinbo, M.R.
    Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme (2003), Nat. Struct. Biol., 10, 349-356.
    View publication on PubMed

Application

EC Number Application Comment Organism
3.1.1.1 medicine the bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.1.1.1 crystallized in the presence of either 10 mM naloxone methiodide or 100 mM homatropine using sitting drop vapor diffusion at 22°C. Overview of hCE1 structures, crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide 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 Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.1.1.1 (R)-cocaine
-
 Homo sapiens
3.1.1.1 cocaethylene
-
 Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
3.1.1.1 Homo sapiens P23141
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
3.1.1.1 glycoprotein
-
 Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.1.1 6-monoacetylmorphine + H2O hCE1 can metabolize the conversion of heroin to both 6-monoacetylmorphine and morphine. hCE1 is able to catalyze both reactions, but it is more efficient at the hydrolysis of heroin to 6-monoacetylmorphine, the first step of heroin metabolism Homo sapiens morphine + acetate
-
 ?
3.1.1.1 cocaine + H2O the enzyme is site- and stereospecific for hydrolysis and transesterification of the methyl ester linkage on R-cocaine Homo sapiens O-benzoylecgonine + methanol
-
 ?
3.1.1.1 heroin + H2O hCE1 can metabolize the conversion of heroin to both 6-monoacetylmorphine and morphine. hCE1 is able to catalyze both reactions, but it is more efficient at the hydrolysis of heroin to 6-monoacetylmorphine, the first step of heroin metabolism Homo sapiens 6-monoacetylmorphine + acetate
-
 ?
3.1.1.1 additional information hCE1 catalyzes the transesterification of cocaine with ethanol to generate cocaethylene. 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. hCE1 prefers methyl ester- or acetyl-type linkages within its small, rigid pocket and bulky groups within the large, flexible pocket. The small, rigid pocket in hCE1 is selective, whereas its large, flexible pocket is promiscuous with regard to substrate specificity. Together, these pockets allow hCE1 to act on structurally distinct compounds containing either large or small alcohol substituent groups Homo sapiens ?
-
 ?

Subunits

EC Number Subunits Comment Organism
3.1.1.1 hexamer trimer-hexamer equilibrium Homo sapiens
3.1.1.1 trimer trimer-hexamer equilibrium Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
3.1.1.1 carboxylesterase 1
-
 Homo sapiens
3.1.1.1 HCE1
-
 Homo sapiens