Literature summary for 3.1.1.1 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.

Application

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

Crystallization (Commentary)

Crystallization (Comment)	Organism
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

Crystallization (Comment)

Organism

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

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P23141	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
glycoprotein	-	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
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	-	?
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	-	?
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	-	?
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

Subunits	Comment	Organism
hexamer	trimer-hexamer equilibrium	Homo sapiens
trimer	trimer-hexamer equilibrium	Homo sapiens

Synonyms

Synonyms	Comment	Organism
carboxylesterase 1	-	Homo sapiens
HCE1	-	Homo sapiens