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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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EC Tree
     3 Hydrolases
         3.1 Acting on ester bonds
             3.1.1 Carboxylic-ester hydrolases
                3.1.1.84 cocaine esterase
IUBMB 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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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: O00748
Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
cocaine esterase, cocaine hydrolase, coch1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6-MAM hydrolyse
281852
-
butyrylcholinesterase
247
-
cocaine hydrolase
281852
-
CocH1
281852
-
hCE-2
281852
-
heroin hydrolyse
281852
-
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) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(-)-cocaine + H2O
ecgonine methyl ester + benzoate
show the reaction diagram
-
-
-
?
4-methylumbelliferyl acetate + H2O
4-methylumbelliferone + acetate
show the reaction diagram
hCE-2 has higher catalytic efficiency for hydrolysis than hCE-1
-
-
?
6-monoacetylmorphine + H2O
morphine + acetate
show the reaction diagram
cocaine + H2O
ecgonine methyl ester + benzoate
show the reaction diagram
heroin + H2O
6-monoacetylmorphine + acetate
show the reaction diagram
(-)-cocaine + H2O
benzoic acid + methyl (1R,2R,3S,5S)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]-octane-2-carboxylate
show the reaction diagram
-
-
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
show the reaction diagram
-
-
i.e. ecgonine methyl ester
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
6-monoacetylmorphine + H2O
morphine + acetate
show the reaction diagram
-
-
-
?
cocaine + H2O
ecgonine methyl ester + benzoate
show the reaction diagram
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
-
-
?
heroin + H2O
6-monoacetylmorphine + acetate
show the reaction diagram
-
-
-
?
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 hide
LITERATURE
IMAGE
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
0.245 - 6.8
heroin
0.0011 - 0.0045
(-)-cocaine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0001
eserine
-
additional information
additional information
inhibition kinetics, kinetic modelling, overview
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.9
isoelectric focusing
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
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?
EST2_HUMAN
559
0
61807
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60000
1 * 60000, SDS-PAGE
80000
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
1 * 60000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
high mannose type
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
QFF resin anion-exchange chromatography and Hypatite C column chromatography
-
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
expressed in HEK-293T/17 cells
-
wild type and mutant enzymes are expressed in HEK-293T/17 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)
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
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