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EC Tree
IUBMB Comments Rhodococcus sp. strain MB1 and Pseudomonas maltophilia strain MB11L can utilize cocaine as sole source of carbon and energy [2,3].
The taxonomic range for the selected organisms is: Homo sapiens The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
cocaine esterase, cocaine hydrolase, coch1,
more
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butyrylcholinesterase
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cocaine benzoylhydrolase
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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(-)-cocaine + H2O
ecgonine methyl ester + benzoate
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4-methylumbelliferyl acetate + H2O
4-methylumbelliferone + acetate
hCE-2 has higher catalytic efficiency for hydrolysis than hCE-1
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?
6-monoacetylmorphine + H2O
morphine + acetate
cocaine + H2O
ecgonine methyl ester + benzoate
heroin + H2O
6-monoacetylmorphine + acetate
(-)-cocaine + H2O
benzoic acid + methyl (1R,2R,3S,5S)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]-octane-2-carboxylate
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i.e. ecgonine methyl ester
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?
(-)-cocaine + H2O
benzoic acid + methyl-(1R,2R,3S,5S)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]-octane-2-carboxylate
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i.e. ecgonine methyl ester
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?
additional information
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6-monoacetylmorphine + H2O
morphine + acetate
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-
-
?
6-monoacetylmorphine + H2O
morphine + acetate
hCE-2 has higher catalytic efficiency for hydrolysis than hCE-1
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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
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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
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?
heroin + H2O
6-monoacetylmorphine + acetate
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-
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?
heroin + H2O
6-monoacetylmorphine + acetate
hCE-2 has higher catalytic efficiency for hydrolysis than hCE-1
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?
additional information
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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)
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additional information
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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)
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6-monoacetylmorphine + H2O
morphine + acetate
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?
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
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?
heroin + H2O
6-monoacetylmorphine + acetate
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?
additional information
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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)
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eserine
hCE-2 shows greater inhibition by eserine thann hCE-1
additional information
potential inhibitory activity of heroin or 6-monoacetylmorphine against CocH1-catalyzed hydrolysis of another substrate like (-)-cocaine
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Cardiotoxicity
Cocaine Hydrolase Gene Transfer Demonstrates Cardiac Safety and Efficacy against Cocaine-Induced QT Prolongation in Mice.
Seizures
A Bacterial Cocaine Esterase Protects Against Cocaine-Induced Epileptogenic Activity and Lethality.
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0.0031
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
0.15
4-yethylumbelliferyl acetate
pH 7.4, 37°C
0.13 - 0.292
6-monoacetylmorphine
0.39
cocaine
pH 7.4, 37°C
0.0011 - 0.0045
(-)-cocaine
0.13
6-monoacetylmorphine
pH 7.4, 37°C
0.292
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
0.245
heroin
recombinant enzyme, pH 7.4, 37°C
0.0011
(-)-cocaine
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mutant enzyme A199S/F227A/S287G/A328W/E441D, pH not specified in the publication, at 25°C
0.0031
(-)-cocaine
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mutant enzyme A199S/S287G/A328W/Y332G, at 25°C, in 0.1 M potassium phosphate, pH 7.5
0.0031
(-)-cocaine
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mutant enzyme A199S/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
0.0035
(-)-cocaine
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mutant enzyme A199S/F227A/S287G/A328W/Y332G/E441D, pH not specified in the publication, at 25°C
0.0045
(-)-cocaine
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wild type enzyme, pH not specified in the publication, at 25°C
0.0045
(-)-cocaine
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wild type enzyme, at 25°C, in 0.1 M potassium phosphate, pH 7.5
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51
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
0.0037
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
35.8
heroin
recombinant enzyme, pH 7.4, 37°C
0.002 - 73.83
(-)-cocaine
0.002
(-)-cocaine
-
wild type enzyme, pH not specified in the publication, at 25°C
0.068
(-)-cocaine
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wild type enzyme, at 25°C, in 0.1 M potassium phosphate, pH 7.5
28.83
(-)-cocaine
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mutant enzyme A199S/F227A/S287G/A328W/E441D, pH not specified in the publication, at 25°C
51
(-)-cocaine
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mutant enzyme A199S/S287G/A328W/Y332G, at 25°C, in 0.1 M potassium phosphate, pH 7.5
51
(-)-cocaine
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mutant enzyme A199S/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
73.83
(-)-cocaine
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mutant enzyme A199S/F227A/S287G/A328W/Y332G/E441D, pH not specified in the publication, at 25°C
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16452
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
0.0005
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
0.013
heroin
recombinant enzyme, pH 7.4, 37°C
15.17 - 30000
(-)-cocaine
15.17
(-)-cocaine
-
wild type enzyme, at 25°C, in 0.1 M potassium phosphate, pH 7.5
15.17
(-)-cocaine
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wild type enzyme, pH not specified in the publication, at 25°C
141.7
(-)-cocaine
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mutant enzyme A328W/Y332A, pH not specified in the publication, at 25°C
233.3
(-)-cocaine
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mutant enzyme A328W/Y332G, pH not specified in the publication, at 25°C
516.7
(-)-cocaine
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mutant enzyme F227A/S287G/A328W/Y332M, pH not specified in the publication, at 25°C
16500
(-)-cocaine
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mutant enzyme A199S/S287G/A328W/Y332G, at 25°C, in 0.1 M potassium phosphate, pH 7.5
16500
(-)-cocaine
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mutant enzyme A199S/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
16670
(-)-cocaine
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mutant enzyme A199S/F227L/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
18330
(-)-cocaine
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mutant enzyme A199S/F227I/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
21670
(-)-cocaine
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mutant enzyme A199S/F227A/S287G/A328W/Y332G/E441D, pH not specified in the publication, at 25°C
23330
(-)-cocaine
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mutant enzyme A199S/F227V/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
26670
(-)-cocaine
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mutant enzyme A199S/F227A/S287G/A328W/E441D, pH not specified in the publication, at 25°C
30000
(-)-cocaine
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mutant enzyme A199S/F227A/S287G/A328W/Y332G, pH not specified in the publication, at 25°C
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additional information
additional information
inhibition kinetics, kinetic modelling, overview
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SwissProt
brenda
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brenda
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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
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EST2_HUMAN
559
0
61807
Swiss-Prot
Mitochondrion (Reliability: 5 )
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60000
1 * 60000, SDS-PAGE
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monomer
1 * 60000, SDS-PAGE
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glycoprotein
high mannose type
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A199S/F227A/S287G/A328W/E441D
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the mutant shows 1730fold improved (-)-cocaine-hydrolyzing activity compared to the wild type enzyme
A199S/F227A/S287G/A328W/Y332G
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the mutant has a 2020fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/F227A/S287G/A328W/Y332G/E441D
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the mutant shows 1390fold improved (-)-cocaine-hydrolyzing activity compared to the wild type enzyme
A199S/F227A/S287G/A328W/Y332G/F329V
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the mutant has a 121fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/F227I/S287G/A328W/Y332G
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the mutant has a 1170fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/F227L/S287G/A328W/Y332G
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the mutant has a 1130fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/F227V/S287G/A328W/Y332G
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the mutant has a 1490fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/S287G/A328W/Y332G/L286I
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the mutant has a 242fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A328W/Y332A
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the mutant has a 9.4fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A328W/Y332G
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the mutant has a 15fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
F227A/S287G/A328W/Y332M
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the mutant has a 34fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/S287G/A328W/Y332G
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the mutant has a 1080fold improved catalytic efficiency against (-)-cocaine compared to the wild type enzyme
A199S/S287G/A328W/Y332G
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the mutant shows 1080fold improved (-)-cocaine-hydrolyzing activity compared to the wild type enzyme
A199S/S287G/A328W/Y332G
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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
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QFF resin anion-exchange chromatography and Hypatite C column chromatography
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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
expressed in HEK-293T/17 cells
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wild type and mutant enzymes are expressed in HEK-293T/17 cells
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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)
brenda
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
brenda
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
brenda
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
brenda
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)
brenda