BRENDA - Enzyme Database show
show all sequences of 3.1.1.84

Kinetic characterization of cholinesterases and a therapeutically valuable cocaine hydrolase for their catalytic activities against heroin and its metabolite 6-monoacetylmorphine

Kim, K.; Yao, J.; Jin, Z.; Zheng, F.; Zhan, C.G.; Chem. Biol. Interact. 293, 107-114 (2018)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
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
Homo sapiens
Inhibitors
Inhibitors
Commentary
Organism
Structure
additional information
potential inhibitory activity of heroin or 6-monoacetylmorphine against CocH1-catalyzed hydrolysis of another substrate like (-)-cocaine
Homo sapiens
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.0031
-
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
0.245
-
heroin
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
0.292
-
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
6-monoacetylmorphine + H2O
Homo sapiens
-
morphine + acetate
-
-
?
heroin + H2O
Homo sapiens
-
6-monoacetylmorphine + acetate
-
-
?
additional information
Homo sapiens
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)
?
-
-
-
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
O00748
-
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
(-)-cocaine + H2O
-
750291
Homo sapiens
ecgonine methyl ester + benzoate
-
-
-
?
6-monoacetylmorphine + H2O
-
750291
Homo sapiens
morphine + acetate
-
-
-
?
heroin + H2O
-
750291
Homo sapiens
6-monoacetylmorphine + acetate
-
-
-
?
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)
750291
Homo sapiens
?
-
-
-
-
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)
750291
Homo sapiens
?
-
-
-
-
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.0037
-
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
35.8
-
heroin
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
51
-
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.4
-
assay at
Homo sapiens
Ki Value [mM]
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
additional information
-
additional information
inhibition kinetics, kinetic modelling, overview
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
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
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
additional information
potential inhibitory activity of heroin or 6-monoacetylmorphine against CocH1-catalyzed hydrolysis of another substrate like (-)-cocaine
Homo sapiens
Ki Value [mM] (protein specific)
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
additional information
-
additional information
inhibition kinetics, kinetic modelling, overview
Homo sapiens
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.0031
-
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
0.245
-
heroin
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
0.292
-
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
6-monoacetylmorphine + H2O
Homo sapiens
-
morphine + acetate
-
-
?
heroin + H2O
Homo sapiens
-
6-monoacetylmorphine + acetate
-
-
?
additional information
Homo sapiens
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)
?
-
-
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
(-)-cocaine + H2O
-
750291
Homo sapiens
ecgonine methyl ester + benzoate
-
-
-
?
6-monoacetylmorphine + H2O
-
750291
Homo sapiens
morphine + acetate
-
-
-
?
heroin + H2O
-
750291
Homo sapiens
6-monoacetylmorphine + acetate
-
-
-
?
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)
750291
Homo sapiens
?
-
-
-
-
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)
750291
Homo sapiens
?
-
-
-
-
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.0037
-
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
35.8
-
heroin
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
51
-
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.4
-
assay at
Homo sapiens
General Information
General Information
Commentary
Organism
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
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
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
Homo sapiens
KCat/KM [mM/s]
kcat/KM Value [1/mMs-1]
kcat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
0.0005
-
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
0.013
-
heroin
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
16452
-
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
KCat/KM [mM/s] (protein specific)
KCat/KM Value [1/mMs-1]
KCat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
0.0005
-
6-monoacetylmorphine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
0.013
-
heroin
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
16452
-
(-)-cocaine
recombinant enzyme, pH 7.4, 37°C
Homo sapiens
Other publictions for EC 3.1.1.84
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
750291
Kim
Kinetic characterization of c ...
Homo sapiens
Chem. Biol. Interact.
293
107-114
2018
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1
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1
3
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1
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3
1
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1
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1
3
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3
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5
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1
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3
1
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1
1
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3
3
728856
Fang
Rational design, preparation, ...
Rhodococcus sp., Rhodococcus sp. MB1 Bresler
ACS Chem. Biol.
9
1764-1772
2014
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1
1
3
-
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3
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2
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3
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2
1
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3
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3
3
730250
Brim
The fate of bacterial cocaine ...
Rhodococcus sp.
J. Pharmacol. Exp. Ther.
340
83-95
2012
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1
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1
1
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-
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-
730421
Lee
Cell permeable cocaine esteras ...
Rhodococcus sp., Rhodococcus sp. MB1
Mol. Pharm.
9
1361-1373
2012
-
-
1
-
5
-
-
6
-
-
1
2
-
6
-
-
1
-
-
-
-
-
2
1
-
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1
6
-
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1
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5
-
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6
-
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1
2
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1
-
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2
1
-
-
1
6
-
-
-
-
-
-
-
-
6
6
716278
Xue
Design, preparation, and chara ...
Homo sapiens
Mol. Pharmacol.
79
290-297
2011
-
-
1
-
3
-
-
4
-
-
-
-
-
1
-
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1
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1
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1
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4
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1
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3
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4
-
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1
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1
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1
-
-
-
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4
-
-
-
-
-
-
-
-
4
4
716281
Narasimhan
Subunit stabilization and pegy ...
Rhodococcus sp.
Mol. Pharmacol.
80
1056-1065
2011
-
-
1
1
3
-
-
4
-
-
1
-
-
3
-
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1
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1
1
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1
4
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1
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3
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4
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1
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1
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1
1
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1
4
-
-
-
-
-
-
-
-
4
4
714226
Zheng
Design of high-activity mutant ...
Homo sapiens
Biochemistry
49
9113-9119
2010
-
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1
1
10
-
-
-
-
-
-
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-
1
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1
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1
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1
10
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1
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9
9
714702
Yang
Characterization of a high-act ...
Homo sapiens
Chem. Biol. Interact.
187
148-152
2010
-
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1
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2
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1
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1
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2
-
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-
-
2
2
716276
Brim
A thermally stable form of bac ...
Rhodococcus sp., Rhodococcus sp. MB1
Mol. Pharmacol.
77
593-600
2010
-
1
-
1
1
-
-
4
-
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7
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1
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2
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1
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716824
Narasimhan
Structural analysis of thermos ...
Rhodococcus sp., Rhodococcus sp. MB1
Protein Eng.
23
537-547
2010
-
1
1
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5
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4
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6
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1
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1
5
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5
5
692028
Ko
Effects of cocaine esterase fo ...
Rhodococcus sp.
Drug Alcohol Depend.
101
202-209
2009
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1
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694267
Gao
Thermostable variants of cocai ...
Rhodococcus sp.
Mol. Pharmacol.
75
318-323
2009
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1
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4
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3
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1
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1
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4
1
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699760
Collins
Zhan. C.G.; Woods. J.H.: Cocai ...
Rhodococcus sp.
J. Pharmacol. Exp. Ther.
331
445-455
2009
-
1
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1
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4
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-
698483
Liu
Fundamental reaction mechanism ...
Rhodococcus sp.
J. Am. Chem. Soc.
131
11964-11975
2003
-
-
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-
-
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-
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1
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1
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1
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2
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650108
Turner
Biochemical characterization a ...
Rhodococcus sp.
Biochemistry
41
12297-12307
2002
-
1
1
1
11
-
-
10
-
-
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1
1
2
-
-
-
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-
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3
-
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9
1
1
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1
1
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1
11
-
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10
-
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1
1
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3
-
-
-
-
9
1
1
-
-
-
-
-
-
-
-
653322
Larsen
Crystal structure of a bacteri ...
Rhodococcus sp.
Nat. Struct. Biol.
9
17-21
2002
-
1
-
1
-
-
-
-
-
-
-
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1
-
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