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Information on EC 3.1.1.84 - cocaine esterase and Organism(s) Homo sapiens and UniProt Accession O00748
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3.1.1.84 cocaine esteraseIUBMB Comments
Rhodococcus sp. strain MB1 and Pseudomonas maltophilia strain MB11L can utilize cocaine as sole source of carbon and energy [2,3].
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Word Map
- 3.1.1.84
- butyrylcholinesterase
-
addict
-
abuse
-
cocaine-induced
-
overdose
-
cochs
- ecgonine
-
self-administration
-
cocaine-metabolizing
- medicine
- benzoylecgonine
-
helper-dependent
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anticocaine
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fc-fused
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drug-seeking
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norcocaine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
cocaine esterase, cocaine hydrolase, coch1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
cocaine benzoylhydrolase
Rhodococcus sp. strain MB1 and Pseudomonas maltophilia strain MB11L can utilize cocaine as sole source of carbon and energy [2,3].
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-methylumbelliferyl acetate + H2O
4-methylumbelliferone + acetate
hCE-2 has higher catalytic efficiency for hydrolysis than hCE-1
-
-
?
(-)-cocaine + H2O
benzoic acid + methyl (1R,2R,3S,5S)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]-octane-2-carboxylate
-
-
i.e. ecgonine methyl ester
-
?
(-)-cocaine + H2O
benzoic acid + methyl-(1R,2R,3S,5S)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]-octane-2-carboxylate
-
-
i.e. ecgonine methyl ester
-
?
6-monoacetylmorphine + H2O
morphine + acetate
hCE-2 has higher catalytic efficiency for hydrolysis than hCE-1
-
-
?
cocaine + H2O
ecgonine methyl ester + benzoate
hCE-2 exhibits different drug ester substrate specificity from the human liver carboxylesterase hCE-1, which hydrolyzes the methyl ester of cocaine. hCE-2 may play an important role in the degradation of cocaine and heroin in human tissues
-
-
?
cocaine + H2O
ecgonine methyl ester + benzoate
hCE-2 exhibits different drug ester substrate specificity from the human liver carboxylesterase hCE-1, which hydrolyzes the methyl ester of cocaine
-
-
?
heroin + H2O
6-monoacetylmorphine + acetate
hCE-2 has higher catalytic efficiency for hydrolysis than hCE-1
-
-
?
additional information
?
-
heroin hydrolysis to 6-MAM and morphine is accelerated by cholinesterases, including acetylcholinesterase (AChE, EC 3.1.1.7) and/or butyrylcholinesterase (BChE, EC 3.1.1.8)
-
-
?
additional information
?
-
the enzyme activity for converting 6-monoacetylmorphine to morphine is much lower than that for converting heroin to 6-monoacetylmorphine. Substrate specificities compared to acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8)
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
cocaine + H2O
ecgonine methyl ester + benzoate
hCE-2 exhibits different drug ester substrate specificity from the human liver carboxylesterase hCE-1, which hydrolyzes the methyl ester of cocaine. hCE-2 may play an important role in the degradation of cocaine and heroin in human tissues
-
-
?
additional information
?
-
heroin hydrolysis to 6-MAM and morphine is accelerated by cholinesterases, including acetylcholinesterase (AChE, EC 3.1.1.7) and/or butyrylcholinesterase (BChE, EC 3.1.1.8)
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
potential inhibitory activity of heroin or 6-monoacetylmorphine against CocH1-catalyzed hydrolysis of another substrate like (-)-cocaine
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0011
(-)-cocaine
-
mutant enzyme A199S/F227A/S287G/A328W/E441D, pH not specified in the publication, at 25°C
0.0031
(-)-cocaine
-
mutant enzyme A199S/S287G/A328W/Y332G, at 25°C, in 0.1 M potassium phosphate, pH 7.5
0.0031
(-)-cocaine
-
mutant enzyme A199S/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
0.0035
(-)-cocaine
-
mutant enzyme A199S/F227A/S287G/A328W/Y332G/E441D, pH not specified in the publication, at 25°C
0.0045
(-)-cocaine
-
wild type enzyme, pH not specified in the publication, at 25°C
0.0045
(-)-cocaine
-
wild type enzyme, at 25°C, in 0.1 M potassium phosphate, pH 7.5
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
(-)-cocaine
-
wild type enzyme, pH not specified in the publication, at 25°C
0.068
(-)-cocaine
-
wild type enzyme, at 25°C, in 0.1 M potassium phosphate, pH 7.5
28.83
(-)-cocaine
-
mutant enzyme A199S/F227A/S287G/A328W/E441D, pH not specified in the publication, at 25°C
51
(-)-cocaine
-
mutant enzyme A199S/S287G/A328W/Y332G, at 25°C, in 0.1 M potassium phosphate, pH 7.5
51
(-)-cocaine
-
mutant enzyme A199S/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
73.83
(-)-cocaine
-
mutant enzyme A199S/F227A/S287G/A328W/Y332G/E441D, pH not specified in the publication, at 25°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
15.17
(-)-cocaine
-
wild type enzyme, at 25°C, in 0.1 M potassium phosphate, pH 7.5
15.17
(-)-cocaine
-
wild type enzyme, pH not specified in the publication, at 25°C
141.7
(-)-cocaine
-
mutant enzyme A328W/Y332A, pH not specified in the publication, at 25°C
233.3
(-)-cocaine
-
mutant enzyme A328W/Y332G, pH not specified in the publication, at 25°C
516.7
(-)-cocaine
-
mutant enzyme F227A/S287G/A328W/Y332M, pH not specified in the publication, at 25°C
16500
(-)-cocaine
-
mutant enzyme A199S/S287G/A328W/Y332G, at 25°C, in 0.1 M potassium phosphate, pH 7.5
16500
(-)-cocaine
-
mutant enzyme A199S/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
16670
(-)-cocaine
-
mutant enzyme A199S/F227L/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
18330
(-)-cocaine
-
mutant enzyme A199S/F227I/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
21670
(-)-cocaine
-
mutant enzyme A199S/F227A/S287G/A328W/Y332G/E441D, pH not specified in the publication, at 25°C
23330
(-)-cocaine
-
mutant enzyme A199S/F227V/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
26670
(-)-cocaine
-
mutant enzyme A199S/F227A/S287G/A328W/E441D, pH not specified in the publication, at 25°C
30000
(-)-cocaine
-
mutant enzyme A199S/F227A/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
inhibition kinetics, kinetic modelling, overview
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
enzyme structure homology modelling, molecular dynamics simulations on the structures of enzyme-substrate complexes using the crystal structures of AChE (PDB ID 1B41), and BChE (PDB IDs 2XQF and 1P0P), molecular docking, overview. The positively charged amino-group of the substrates (heroin and 6-monoacetylmorphine) is placed in the choline-binding site near Trp82 in BChE and CocH1 or Trp86 in AChE. The binding models of heroin and 6-monoacetylmorphine in the corresponding enzyme-substrate complexes are optimized by performing the energy minimization
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). EST2_HUMAN
559
0
61807
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A199S/F227A/S287G/A328W/E441D
-
the mutant shows 1730fold improved (-)-cocaine-hydrolyzing activity compared to the wild type enzyme
A199S/F227A/S287G/A328W/Y332G
-
the mutant has a 2020fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/F227A/S287G/A328W/Y332G/E441D
-
the mutant shows 1390fold improved (-)-cocaine-hydrolyzing activity compared to the wild type enzyme
A199S/F227A/S287G/A328W/Y332G/F329V
-
the mutant has a 121fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/F227I/S287G/A328W/Y332G
-
the mutant has a 1170fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/F227L/S287G/A328W/Y332G
-
the mutant has a 1130fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/F227V/S287G/A328W/Y332G
-
the mutant has a 1490fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/S287G/A328W/Y332G
A199S/S287G/A328W/Y332G/L286I
-
the mutant has a 242fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A328W/Y332A
-
the mutant has a 9.4fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A328W/Y332G
-
the mutant has a 15fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
F227A/S287G/A328W/Y332M
-
the mutant has a 34fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/S287G/A328W/Y332G
-
the mutant has a 1080fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/S287G/A328W/Y332G
-
the mutant shows 1080fold improved (-)-cocaine-hydrolyzing activity compared to the wild type enzyme
A199S/S287G/A328W/Y332G
-
the mutant shows high activity towards (-)-cocaine with about 1080fold (un-fused) and 100fold (when fused with human serum albumin) improved catalytic efficiency compared to the wild type enzyme and also leads to a decrease in catalytic efficiency with acetylthiocholine and butyrylthiocholine
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme CocH1, the A199S/F227A/S287G/A328W mutant of human BChE (EC 3.1.1.8) containing C-terminal human serum albumin (HSA) is generated and cloned in to pCMV-MCS and expressed in CHO-S cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pindel, E.V.; Kedishvili, N.Y.; Abraham, T.L.; Brzezinski, M.R.; Zhang, J.; Dean, R.A.; Bosron, W.F.
Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin
J. Biol. Chem.
272
14769-14775
1997
Homo sapiens (O00748)
Zheng, F.; Yang, W.; Xue, L.; Hou, S.; Liu, J.; Zhan, C.
Design of high-activity mutants of human butyrylcholinesterase against (-)-cocaine: Structural and energetic factors affecting the catalytic efficiency
Biochemistry
49
9113-9119
2010
Homo sapiens
Yang, W.; Xue, L.; Fang, L.; Chen, X.; Zhan, C.
Characterization of a high-activity mutant of human butyrylcholinesterase against (-)-cocaine
Chem. Biol. Interact.
187
148-152
2010
Homo sapiens
Xue, L.; Ko, M.; Tong, M.; Yang, W.; Hou, S.; Fang, L.; Liu, J.; Zheng, F.; Woods, J.; Tai, H.; Zhan, C.
Design, preparation, and characterization of high-activity mutants of human butyrylcholinesterase specific for detoxification of cocaine
Mol. Pharmacol.
79
290-297
2011
Homo sapiens
Kim, K.; Yao, J.; Jin, Z.; Zheng, F.; Zhan, C.G.
Kinetic characterization of cholinesterases and a therapeutically valuable cocaine hydrolase for their catalytic activities against heroin and its metabolite 6-monoacetylmorphine
Chem. Biol. Interact.
293
107-114
2018
Homo sapiens (O00748)
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