BRENDA - Enzyme Database show
show all sequences of 1.1.1.236

Tropinone reductases, enzymes at the branch point of tropane alkaloid metabolism

Draeger, B.; Phytochemistry 67, 327-337 (2006)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
expressed in Escherichia coli
Atropa belladonna
expressed in Escherichia coli
Datura stramonium
expressed in Escherichia coli
Hyoscyamus niger
expressed in Escherichia coli
Solanum tuberosum
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.002
-
NADPH
-
Solanum tuberosum
0.0021
-
NADPH
-
Atropa belladonna
0.0061
-
NADPH
-
Hyoscyamus niger
0.016
-
NADPH
at pH 5.95
Datura stramonium
0.033
-
tropinone
at pH 5.95
Datura stramonium
0.033
-
tropinone
at pH 6.4
Solanum tuberosum
0.034
-
tropinone
at pH 5.9
Hyoscyamus niger
0.09
-
tropinone
at pH 6.25
Atropa belladonna
0.265
-
N-propyl-4-piperidinone
-
Hyoscyamus niger
0.38
-
4-tetrahydro-thiopyranone
-
Atropa belladonna
0.534
-
4-ethyl-cyclohexanone
-
Hyoscyamus niger
0.65
-
N-methyl-4-piperidinone
-
Atropa belladonna
0.77
-
N-methyl-4-piperidinone
-
Hyoscyamus niger
2
-
4-tetrahydro-thiopyranone
-
Datura stramonium
2.03
-
4-methyl-cyclohexanone
-
Hyoscyamus niger
2.8
-
4-methyl-cyclohexanone
-
Datura stramonium
7.58
-
3-methyl-cyclohexanone
-
Hyoscyamus niger
20
-
N-methyl-4-piperidinone
-
Datura stramonium
Molecular Weight [Da]
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
28310
-
calculation from sequence of cDNA
Atropa belladonna
28310
-
calculation from sequence of cDNA
Datura stramonium
28310
-
calculation from sequence of cDNA
Hyoscyamus niger
28310
-
calculation from sequence of cDNA
Solanum tuberosum
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Atropa belladonna
-
-
-
Datura stramonium
-
-
-
Hyoscyamus niger
-
-
-
Solanum tuberosum
-
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
root
-
Atropa belladonna
-
root
-
Datura stramonium
-
root
-
Hyoscyamus niger
-
root
-
Solanum tuberosum
-
Specific Activity [micromol/min/mg]
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
additional information
-
quinuclidinone and 8-thiabicylo[3.2.1]octan-3-one are no substrates of TRII
Atropa belladonna
additional information
-
quinuclidinone and 8-thiabicylo[3.2.1]octan-3-one are no substrates of TRII
Datura stramonium
additional information
-
quinuclidinone and 8-thiabicylo[3.2.1]octan-3-one are no substrates of TRII
Hyoscyamus niger
additional information
-
quinuclidinone and 8-thiabicylo[3.2.1]octan-3-one are no substrates of TRII
Solanum tuberosum
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3-methyl-cyclohexanone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
4-ethyl-cyclohexanone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
4-methyl-cyclohexanone + NADPH
-
670518
Datura stramonium
? + NADP+
-
-
-
?
4-methyl-cyclohexanone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
4-tetrahydro-thiopyranone + NADP+
-
670518
Datura stramonium
? + NADP+
-
-
-
?
4-tetrahydro-thiopyranone + NADPH
-
670518
Atropa belladonna
? + NADP+
-
-
-
?
N-methyl-4-piperidinone + NADPH
-
670518
Datura stramonium
? + NADP+
-
-
-
?
N-methyl-4-piperidinone + NADPH
-
670518
Atropa belladonna
? + NADP+
-
-
-
?
N-methyl-4-piperidinone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
N-propyl-4-piperidinone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
tropinone + NADPH + H+
-
670518
Solanum tuberosum
pseudotropine + NADP+
-
-
-
ir
tropinone + NADPH + H+
-
670518
Datura stramonium
pseudotropine + NADP+
-
-
-
ir
tropinone + NADPH + H+
-
670518
Atropa belladonna
pseudotropine + NADP+
-
-
-
ir
tropinone + NADPH + H+
-
670518
Hyoscyamus niger
pseudotropine + NADP+
-
-
-
ir
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
2.73
-
tropinone
at pH 7.0
Datura stramonium
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
5
-
-
Solanum tuberosum
5.8
-
-
Hyoscyamus niger
6.25
-
-
Atropa belladonna
6.25
-
-
Datura stramonium
Cofactor
Cofactor
Commentary
Organism
Structure
NADPH
-
Atropa belladonna
NADPH
-
Datura stramonium
NADPH
-
Hyoscyamus niger
NADPH
-
Solanum tuberosum
Cloned(Commentary) (protein specific)
Commentary
Organism
expressed in Escherichia coli
Atropa belladonna
expressed in Escherichia coli
Datura stramonium
expressed in Escherichia coli
Hyoscyamus niger
expressed in Escherichia coli
Solanum tuberosum
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
NADPH
-
Atropa belladonna
NADPH
-
Datura stramonium
NADPH
-
Hyoscyamus niger
NADPH
-
Solanum tuberosum
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.002
-
NADPH
-
Solanum tuberosum
0.0021
-
NADPH
-
Atropa belladonna
0.0061
-
NADPH
-
Hyoscyamus niger
0.016
-
NADPH
at pH 5.95
Datura stramonium
0.033
-
tropinone
at pH 5.95
Datura stramonium
0.033
-
tropinone
at pH 6.4
Solanum tuberosum
0.034
-
tropinone
at pH 5.9
Hyoscyamus niger
0.09
-
tropinone
at pH 6.25
Atropa belladonna
0.265
-
N-propyl-4-piperidinone
-
Hyoscyamus niger
0.38
-
4-tetrahydro-thiopyranone
-
Atropa belladonna
0.534
-
4-ethyl-cyclohexanone
-
Hyoscyamus niger
0.65
-
N-methyl-4-piperidinone
-
Atropa belladonna
0.77
-
N-methyl-4-piperidinone
-
Hyoscyamus niger
2
-
4-tetrahydro-thiopyranone
-
Datura stramonium
2.03
-
4-methyl-cyclohexanone
-
Hyoscyamus niger
2.8
-
4-methyl-cyclohexanone
-
Datura stramonium
7.58
-
3-methyl-cyclohexanone
-
Hyoscyamus niger
20
-
N-methyl-4-piperidinone
-
Datura stramonium
Molecular Weight [Da] (protein specific)
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
28310
-
calculation from sequence of cDNA
Atropa belladonna
28310
-
calculation from sequence of cDNA
Datura stramonium
28310
-
calculation from sequence of cDNA
Hyoscyamus niger
28310
-
calculation from sequence of cDNA
Solanum tuberosum
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
root
-
Atropa belladonna
-
root
-
Datura stramonium
-
root
-
Hyoscyamus niger
-
root
-
Solanum tuberosum
-
Specific Activity [micromol/min/mg] (protein specific)
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
additional information
-
quinuclidinone and 8-thiabicylo[3.2.1]octan-3-one are no substrates of TRII
Atropa belladonna
additional information
-
quinuclidinone and 8-thiabicylo[3.2.1]octan-3-one are no substrates of TRII
Datura stramonium
additional information
-
quinuclidinone and 8-thiabicylo[3.2.1]octan-3-one are no substrates of TRII
Hyoscyamus niger
additional information
-
quinuclidinone and 8-thiabicylo[3.2.1]octan-3-one are no substrates of TRII
Solanum tuberosum
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3-methyl-cyclohexanone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
4-ethyl-cyclohexanone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
4-methyl-cyclohexanone + NADPH
-
670518
Datura stramonium
? + NADP+
-
-
-
?
4-methyl-cyclohexanone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
4-tetrahydro-thiopyranone + NADP+
-
670518
Datura stramonium
? + NADP+
-
-
-
?
4-tetrahydro-thiopyranone + NADPH
-
670518
Atropa belladonna
? + NADP+
-
-
-
?
N-methyl-4-piperidinone + NADPH
-
670518
Datura stramonium
? + NADP+
-
-
-
?
N-methyl-4-piperidinone + NADPH
-
670518
Atropa belladonna
? + NADP+
-
-
-
?
N-methyl-4-piperidinone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
N-propyl-4-piperidinone + NADPH
-
670518
Hyoscyamus niger
? + NADP+
-
-
-
?
tropinone + NADPH + H+
-
670518
Solanum tuberosum
pseudotropine + NADP+
-
-
-
ir
tropinone + NADPH + H+
-
670518
Datura stramonium
pseudotropine + NADP+
-
-
-
ir
tropinone + NADPH + H+
-
670518
Atropa belladonna
pseudotropine + NADP+
-
-
-
ir
tropinone + NADPH + H+
-
670518
Hyoscyamus niger
pseudotropine + NADP+
-
-
-
ir
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
2.73
-
tropinone
at pH 7.0
Datura stramonium
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
5
-
-
Solanum tuberosum
5.8
-
-
Hyoscyamus niger
6.25
-
-
Atropa belladonna
6.25
-
-
Datura stramonium
Other publictions for EC 1.1.1.236
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)
726209
Dehghan
An atypical pattern of accumul ...
Hyoscyamus muticus, Hyoscyamus senecionis
Plant Physiol. Biochem.
70C
188-194
2013
-
-
-
-
-
-
-
-
-
-
-
2
-
2
-
-
-
-
-
3
-
-
2
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
3
-
-
2
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
696874
Kai
Molecular cloning, characteriz ...
Anisodus acutangulus
Biotechnol. Appl. Biochem.
54
:177-186
2009
1
-
-
-
-
-
1
-
-
-
1
-
-
1
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
1
-
-
-
-
1
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
689548
Brock
The functional divergence of s ...
Cochlearia officinalis
Plant J.
54
388-401
2008
-
-
1
-
-
-
-
-
-
-
-
2
-
1
-
-
-
-
-
-
-
-
4
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
4
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
689953
Freydank
Protein structure modeling ind ...
Solanum dulcamara
Proteins
72
173-183
2008
-
-
1
-
-
-
-
1
-
-
1
1
-
1
-
-
1
-
-
-
-
-
3
2
1
-
-
-
1
1
-
1
-
-
-
-
-
1
1
-
-
-
-
-
-
1
-
-
1
1
-
-
-
1
-
-
-
-
3
2
1
-
-
-
1
1
-
-
-
-
-
-
-
-
670518
Draeger
Tropinone reductases, enzymes ...
Atropa belladonna, Datura stramonium, Hyoscyamus niger, Solanum tuberosum
Phytochemistry
67
327-337
2006
-
-
4
-
-
-
-
18
-
-
4
-
-
4
-
-
-
-
-
4
4
-
14
-
-
-
-
1
4
-
-
4
-
-
-
-
-
4
4
-
-
-
-
-
-
18
-
-
4
-
-
-
-
-
-
4
4
-
14
-
-
-
-
1
4
-
-
-
-
-
-
-
-
-
670636
Kaiser
Immunolocalisation of two trop ...
Solanum tuberosum
Planta
225
127-137
2006
-
-
1
-
-
-
-
-
-
-
1
-
-
3
-
-
1
-
-
4
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
1
1
-
-
-
-
-
-
-
-
-
1
-
-
-
-
1
-
4
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
656413
Richter
Overexpression of tropinone re ...
Datura stramonium
J. Exp. Bot.
56
645-652
2005
-
-
1
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
1
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
654707
Yamashita
Capturing enzyme structure pri ...
Datura stramonium
Biochemistry
42
5566-5573
2003
-
-
-
-
-
-
-
2
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
348033
Keiner
Molecular cloning, expression ...
Atropa belladonna, Datura stramonium, Hyoscyamus niger, Solanum tuberosum
Plant Mol. Biol.
48
299-308
2002
-
-
2
1
-
-
-
4
-
-
-
4
-
7
-
-
2
-
-
17
-
-
8
-
-
-
-
-
-
-
-
3
-
-
-
-
-
2
3
1
-
-
-
-
-
4
-
-
-
4
-
-
-
2
-
17
-
-
8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
347972
Nakajima
Site-directed mutagenesis of p ...
Arabidopsis sp., Datura stramonium, Hyoscyamus niger
J. Biol. Chem.
274
16563-16568
1999
-
-
3
1
-
-
-
19
-
-
-
2
-
3
-
-
2
-
-
-
-
-
2
3
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
1
-
-
-
-
-
19
-
-
-
2
-
-
-
2
-
-
-
-
2
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
347973
Boswell
Specificities of the enzymes o ...
Brugmansia x candida, Datura stramonium, Datura stramonium D15/5, Hyoscyamus niger
Phytochemistry
52
871-878
1999
-
-
-
-
-
-
-
6
-
-
-
3
-
9
-
-
2
-
-
3
-
-
10
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
6
-
-
-
3
-
-
-
2
-
3
-
-
10
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
348030
Nakajima
Two tropinone reductases, that ...
Atropa belladonna, Datura stramonium, Hyoscyamus niger, no activity in Nicotiana tabacum
Plant Cell Physiol.
40
1099-1107
1999
-
-
2
1
-
-
-
-
-
-
1
3
-
4
-
-
2
-
-
4
-
-
3
3
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
1
-
-
-
-
-
-
-
-
1
3
-
-
-
2
-
4
-
-
3
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
348032
Yamashita
Structure of tropinone reducta ...
Datura stramonium
Biochemistry
38
7630-7637
1999
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
348028
Nakajima
Crystal structures of two trop ...
Datura stramonium, Hyoscyamus niger
Proc. Natl. Acad. Sci. USA
95
4876-4881
1998
-
-
1
1
-
-
-
-
-
-
-
2
-
2
-
-
-
-
-
-
-
-
2
2
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
2
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
348027
Portsteffen
The reduction of tropinone in ...
Atropa belladonna, Datura stramonium
Phytochemistry
37
391-400
1994
-
-
1
-
-
-
-
8
-
-
5
2
-
3
-
-
2
-
-
2
1
-
8
2
-
-
-
-
2
-
1
1
-
-
-
-
-
1
1
-
-
-
-
-
-
8
-
-
5
2
-
-
-
2
-
2
1
-
8
2
-
-
-
-
2
-
1
-
-
-
-
-
-
-
348026
Nakajima
Two tropinone reductases with ...
Atropa belladonna, Datura stramonium, Hyoscyamus niger, no activity in Nicotiana tabacum
Proc. Natl. Acad. Sci. USA
90
9591-9595
1993
-
-
2
-
-
-
-
-
-
-
-
3
-
8
-
-
1
-
-
3
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
1
-
3
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
348023
Draeger
Levels of tropinone reductase ...
Atropa belladonna, Datura inoxia, Datura stramonium, Hyoscyamus niger, Physalis peruviana
Planta
188
581-586
1992
-
-
-
-
-
-
-
1
-
-
-
5
-
6
-
-
2
-
-
4
-
-
7
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
5
-
-
-
2
-
4
-
-
7
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
348024
Hashimoto
Two tropinone reductases with ...
Hyoscyamus niger
Plant Physiol.
100
836-845
1992
-
-
-
-
-
-
-
-
-
-
-
1
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
348025
Portsteffen
-
Two tropinone reducing enzymes ...
Atropa belladonna, Calystegia sepium, Datura inoxia, Datura stramonium, Hyoscyamus bohemicus, Hyoscyamus canariensis, Hyoscyamus muticus, Hyoscyamus niger, Hyoscyamus pusillus, no activity in Brassica campestris, no activity in Browallia americana, no activity in Nicotiana tabacum, Physalis alkekengi, Physalis edulis, Physalis philadelphica, Physochlaina orientalis
Phytochemistry
31
1135-1138
1992
-
-
-
-
-
3
1
16
-
-
4
13
-
16
-
-
2
-
-
12
1
1
30
4
-
-
-
-
2
2
1
2
-
-
-
-
-
-
2
-
-
3
-
1
-
16
-
-
4
13
-
-
-
2
-
12
1
1
30
4
-
-
-
-
2
2
1
-
-
-
-
-
-
-
348022
Couladis
-
Enzymes catalysing the reducti ...
Atropa belladonna, Datura inoxia, Datura stramonium, Hyoscyamus niger
Phytochemistry
30
801-805
1991
-
-
-
-
-
2
-
-
-
-
-
4
-
4
-
-
2
-
-
4
1
-
14
-
1
-
-
-
4
-
-
6
-
-
-
-
-
-
6
-
-
2
-
-
-
-
-
-
-
4
-
-
-
2
-
4
1
-
14
-
1
-
-
-
4
-
-
-
-
-
-
-
-
-
348021
Draeger
-
Purification and characterizat ...
Datura stramonium, Hyoscyamus niger
Agric. Biol. Chem.
52
2663-2667
1988
-
-
-
-
-
-
-
4
-
-
2
2
-
2
-
-
1
-
-
2
1
2
15
2
1
-
1
-
1
-
1
4
-
-
-
-
-
-
4
-
-
-
-
-
-
4
-
-
2
2
-
-
-
1
-
2
1
2
15
2
1
-
1
-
1
-
1
-
-
-
-
-
-
-