BRENDA - Enzyme Database
show all sequences of 4.1.3.16

Structural and biochemical studies of human 4-hydroxy-2-oxoglutarate aldolase: implications for hydroxyproline metabolism in primary hyperoxaluria

Riedel, T.J.; Johnson, L.C.; Knight, J.; Hantgan, R.R.; Holmes, R.P.; Lowther, W.T.; PLoS ONE 6, e26021 (2011)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
expression in Escherichia coli
Homo sapiens
Crystallization (Commentary)
Crystallization
Organism
to 1.97 A resolution, crystal structure of enzyme bound to pyruvate. Modeling of the 4-hydroxy-2-oxoglutarate-Schiff base intermediate and kinetic analyses of site-directed mutants support the importance of Lys196 as the nucleophile, Tyr168 and Ser77 as components of a proton relay, and Asn78 and Ser198 as unique residues that facilitate substrate binding
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
K196A
complete loss of activity
Homo sapiens
N78A
20% of wild-type activity
Homo sapiens
N78Q
4% of wild-type activity
Homo sapiens
N78T
45% of wild-type activity
Homo sapiens
S198A
9% of wild-type activity
Homo sapiens
S198T
18% of wild-type activity
Homo sapiens
S77A
5% of wild-type activity
Homo sapiens
S77T
2% of wild-type activity
Homo sapiens
S77V
2% of wild-type activity
Homo sapiens
Y140F
122% of wild-type activity
Homo sapiens
Y168F
complete loss of activity
Homo sapiens
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.008
-
4-hydroxy-2-oxoglutarate
mutant Y140F, pH 8.5, 37°C
Homo sapiens
0.011
-
4-hydroxy-2-oxoglutarate
wild-type, pH 8.5, 37°C
Homo sapiens
0.016
-
4-hydroxy-2-oxoglutarate
mutant N78T, pH 8.5, 37°C
Homo sapiens
0.044
-
4-hydroxy-2-oxoglutarate
mutant S198A, pH 8.5, 37°C
Homo sapiens
0.058
-
4-hydroxy-2-oxoglutarate
mutant S77T, pH 8.5, 37°C
Homo sapiens
0.066
-
4-hydroxy-2-oxoglutarate
mutant N78A, pH 8.5, 37°C
Homo sapiens
0.077
-
4-hydroxy-2-oxoglutarate
mutant S198T, pH 8.5, 37°C
Homo sapiens
0.082
-
4-hydroxy-2-oxoglutarate
mutant S77V, pH 8.5, 37°C
Homo sapiens
0.084
-
4-hydroxy-2-oxoglutarate
mutant S77A, pH 8.5, 37°C
Homo sapiens
0.281
-
4-hydroxy-2-oxoglutarate
mutant N78Q, pH 8.5, 37°C
Homo sapiens
Molecular Weight [Da]
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
35249
-
and dimer, in equilibrium, 4 * 35249, calculated; and tetramer, in equilibrium, 2 * 35249, calculated
Homo sapiens
97200
-
sedimentation equilibrium centrifugation
Homo sapiens
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
Q86XE5
-
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4-Hydroxy-2-oxoglutarate
-
723542
Homo sapiens
Pyruvate + glyoxylate
-
-
-
r
additional information
enzyme performs a retro-aldol cleavage reaction reminiscent of the trimeric 2-keto-3-deoxy-6-phosphogluconate aldolases
723542
Homo sapiens
?
-
-
-
-
Subunits
Subunits
Commentary
Organism
dimer
and tetramer, in equilibrium, 2 * 35249, calculated
Homo sapiens
tetramer
and dimer, in equilibrium, 4 * 35249, calculated
Homo sapiens
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.8
-
4-hydroxy-2-oxoglutarate
mutant S77T, pH 8.5, 37°C
Homo sapiens
1.2
-
4-hydroxy-2-oxoglutarate
mutant S77V, pH 8.5, 37°C
Homo sapiens
2.4
-
4-hydroxy-2-oxoglutarate
mutant S198A, pH 8.5, 37°C
Homo sapiens
2.5
-
4-hydroxy-2-oxoglutarate
mutant S77A, pH 8.5, 37°C
Homo sapiens
4
-
4-hydroxy-2-oxoglutarate
mutant N78T, pH 8.5, 37°C
Homo sapiens
5.2
-
4-hydroxy-2-oxoglutarate
mutant Y140F, pH 8.5, 37°C
Homo sapiens
6.1
-
4-hydroxy-2-oxoglutarate
wild-type, pH 8.5, 37°C
Homo sapiens
6.2
-
4-hydroxy-2-oxoglutarate
mutant N78Q, pH 8.5, 37°C
Homo sapiens
7.6
-
4-hydroxy-2-oxoglutarate
mutant N78A, pH 8.5, 37°C
Homo sapiens
7.8
-
4-hydroxy-2-oxoglutarate
mutant S198T, pH 8.5, 37°C
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
expression in Escherichia coli
Homo sapiens
Crystallization (Commentary) (protein specific)
Crystallization
Organism
to 1.97 A resolution, crystal structure of enzyme bound to pyruvate. Modeling of the 4-hydroxy-2-oxoglutarate-Schiff base intermediate and kinetic analyses of site-directed mutants support the importance of Lys196 as the nucleophile, Tyr168 and Ser77 as components of a proton relay, and Asn78 and Ser198 as unique residues that facilitate substrate binding
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
K196A
complete loss of activity
Homo sapiens
N78A
20% of wild-type activity
Homo sapiens
N78Q
4% of wild-type activity
Homo sapiens
N78T
45% of wild-type activity
Homo sapiens
S198A
9% of wild-type activity
Homo sapiens
S198T
18% of wild-type activity
Homo sapiens
S77A
5% of wild-type activity
Homo sapiens
S77T
2% of wild-type activity
Homo sapiens
S77V
2% of wild-type activity
Homo sapiens
Y140F
122% of wild-type activity
Homo sapiens
Y168F
complete loss of activity
Homo sapiens
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.008
-
4-hydroxy-2-oxoglutarate
mutant Y140F, pH 8.5, 37°C
Homo sapiens
0.011
-
4-hydroxy-2-oxoglutarate
wild-type, pH 8.5, 37°C
Homo sapiens
0.016
-
4-hydroxy-2-oxoglutarate
mutant N78T, pH 8.5, 37°C
Homo sapiens
0.044
-
4-hydroxy-2-oxoglutarate
mutant S198A, pH 8.5, 37°C
Homo sapiens
0.058
-
4-hydroxy-2-oxoglutarate
mutant S77T, pH 8.5, 37°C
Homo sapiens
0.066
-
4-hydroxy-2-oxoglutarate
mutant N78A, pH 8.5, 37°C
Homo sapiens
0.077
-
4-hydroxy-2-oxoglutarate
mutant S198T, pH 8.5, 37°C
Homo sapiens
0.082
-
4-hydroxy-2-oxoglutarate
mutant S77V, pH 8.5, 37°C
Homo sapiens
0.084
-
4-hydroxy-2-oxoglutarate
mutant S77A, pH 8.5, 37°C
Homo sapiens
0.281
-
4-hydroxy-2-oxoglutarate
mutant N78Q, pH 8.5, 37°C
Homo sapiens
Molecular Weight [Da] (protein specific)
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
35249
-
and dimer, in equilibrium, 4 * 35249, calculated; and tetramer, in equilibrium, 2 * 35249, calculated
Homo sapiens
97200
-
sedimentation equilibrium centrifugation
Homo sapiens
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4-Hydroxy-2-oxoglutarate
-
723542
Homo sapiens
Pyruvate + glyoxylate
-
-
-
r
additional information
enzyme performs a retro-aldol cleavage reaction reminiscent of the trimeric 2-keto-3-deoxy-6-phosphogluconate aldolases
723542
Homo sapiens
?
-
-
-
-
Subunits (protein specific)
Subunits
Commentary
Organism
dimer
and tetramer, in equilibrium, 2 * 35249, calculated
Homo sapiens
tetramer
and dimer, in equilibrium, 4 * 35249, calculated
Homo sapiens
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.8
-
4-hydroxy-2-oxoglutarate
mutant S77T, pH 8.5, 37°C
Homo sapiens
1.2
-
4-hydroxy-2-oxoglutarate
mutant S77V, pH 8.5, 37°C
Homo sapiens
2.4
-
4-hydroxy-2-oxoglutarate
mutant S198A, pH 8.5, 37°C
Homo sapiens
2.5
-
4-hydroxy-2-oxoglutarate
mutant S77A, pH 8.5, 37°C
Homo sapiens
4
-
4-hydroxy-2-oxoglutarate
mutant N78T, pH 8.5, 37°C
Homo sapiens
5.2
-
4-hydroxy-2-oxoglutarate
mutant Y140F, pH 8.5, 37°C
Homo sapiens
6.1
-
4-hydroxy-2-oxoglutarate
wild-type, pH 8.5, 37°C
Homo sapiens
6.2
-
4-hydroxy-2-oxoglutarate
mutant N78Q, pH 8.5, 37°C
Homo sapiens
7.6
-
4-hydroxy-2-oxoglutarate
mutant N78A, pH 8.5, 37°C
Homo sapiens
7.8
-
4-hydroxy-2-oxoglutarate
mutant S198T, pH 8.5, 37°C
Homo sapiens
KCat/KM [mM/s]
kcat/KM Value [1/mMs-1]
kcat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
14
-
4-hydroxy-2-oxoglutarate
mutant S77T, pH 8.5, 37°C
Homo sapiens
15
-
4-hydroxy-2-oxoglutarate
mutant S77V, pH 8.5, 37°C
Homo sapiens
22
-
4-hydroxy-2-oxoglutarate
mutant N78Q, pH 8.5, 37°C
Homo sapiens
30
-
4-hydroxy-2-oxoglutarate
mutant S77A, pH 8.5, 37°C
Homo sapiens
55
-
4-hydroxy-2-oxoglutarate
mutant S198A, pH 8.5, 37°C
Homo sapiens
101
-
4-hydroxy-2-oxoglutarate
mutant S198T, pH 8.5, 37°C
Homo sapiens
115
-
4-hydroxy-2-oxoglutarate
mutant N78A, pH 8.5, 37°C
Homo sapiens
250
-
4-hydroxy-2-oxoglutarate
mutant N78T, pH 8.5, 37°C
Homo sapiens
555
-
4-hydroxy-2-oxoglutarate
wild-type, pH 8.5, 37°C
Homo sapiens
650
-
4-hydroxy-2-oxoglutarate
mutant Y140F, pH 8.5, 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
14
-
4-hydroxy-2-oxoglutarate
mutant S77T, pH 8.5, 37°C
Homo sapiens
15
-
4-hydroxy-2-oxoglutarate
mutant S77V, pH 8.5, 37°C
Homo sapiens
22
-
4-hydroxy-2-oxoglutarate
mutant N78Q, pH 8.5, 37°C
Homo sapiens
30
-
4-hydroxy-2-oxoglutarate
mutant S77A, pH 8.5, 37°C
Homo sapiens
55
-
4-hydroxy-2-oxoglutarate
mutant S198A, pH 8.5, 37°C
Homo sapiens
101
-
4-hydroxy-2-oxoglutarate
mutant S198T, pH 8.5, 37°C
Homo sapiens
115
-
4-hydroxy-2-oxoglutarate
mutant N78A, pH 8.5, 37°C
Homo sapiens
250
-
4-hydroxy-2-oxoglutarate
mutant N78T, pH 8.5, 37°C
Homo sapiens
555
-
4-hydroxy-2-oxoglutarate
wild-type, pH 8.5, 37°C
Homo sapiens
650
-
4-hydroxy-2-oxoglutarate
mutant Y140F, pH 8.5, 37°C
Homo sapiens
Other publictions for EC 4.1.3.16
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)
746867
Schapfl
Extended substrate range of t ...
Escherichia coli
Appl. Microbiol. Biotechnol.
102
8359-8372
2018
-
-
1
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1
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1
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1
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1
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748294
Mdimegh
HOGA1 gene mutations of prima ...
Homo sapiens
J. Clin. Lab. Anal.
31
e22053
2017
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2
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1
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2
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1
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2
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1
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1
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-
-
-
-
-
1
1
-
-
-
747772
MacDonald
Cellular degradation of 4-hyd ...
Homo sapiens
FEBS Lett.
590
1467-1476
2016
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-
1
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1
1
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1
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1
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1
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1
1
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1
1
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1
-
-
-
-
-
-
1
1
-
-
-
746641
Huang
Use of a novel microtitration ...
Bos taurus
Acta Crystallogr. Sect. F
70
1546-1549
2014
-
-
-
1
-
-
-
-
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-
1
1
-
4
-
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1
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1
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1
1
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1
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1
1
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1
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1
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1
1
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-
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-
-
-
-
-
-
-
-
-
721727
Riedel
4-Hydroxy-2-oxoglutarate aldol ...
Homo sapiens
Biochim. Biophys. Acta
1822
1544-1552
2012
-
1
1
-
9
-
-
-
-
-
2
-
-
4
-
-
-
-
-
-
1
-
1
1
-
-
-
-
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-
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-
1
1
-
-
9
-
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-
-
-
-
-
2
-
-
-
-
-
-
-
1
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
728378
Williams
The enzyme 4-hydroxy-2-oxoglut ...
Homo sapiens
Nephrol. Dial. Transplant.
27
3191-3195
2012
-
-
1
-
1
-
-
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1
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2
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1
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1
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1
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1
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1
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1
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1
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-
-
-
-
-
-
-
1
1
-
-
-
723542
Riedel
Structural and biochemical stu ...
Homo sapiens
PLoS ONE
6
e26021
2011
-
-
1
1
11
-
-
10
-
-
2
-
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2
-
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-
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2
2
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-
10
-
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1
-
1
11
-
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-
-
10
-
-
2
-
-
-
-
-
-
-
-
-
2
2
-
-
-
10
-
-
-
-
-
-
-
-
10
10
713711
Belostotsky
Mutations in DHDPSL are respon ...
Homo sapiens
Am. J. Hum. Genet.
87
392-399
2010
-
-
-
-
-
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1
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2
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1
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-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
5255
Dekker
2-keto-4-Hydroxyglutarate aldo ...
Bos taurus
J. Biol. Chem.
267
10507-10514
1992
1
-
-
-
-
-
7
2
-
1
6
-
-
4
-
-
1
-
-
5
1
3
5
1
-
-
-
-
1
2
-
-
-
-
-
1
-
-
-
-
-
-
-
7
-
2
-
1
6
-
-
-
-
1
-
5
1
3
5
1
-
-
-
-
1
2
-
-
-
-
-
-
-
-
5253
Anderson
Rat liver 4-hydroxy-2-ketoglut ...
Rattus norvegicus
Arch. Biochem. Biophys.
236
82-97
1985
-
-
-
-
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10
1
2
1
1
-
-
2
-
-
1
-
-
2
2
-
-
-
1
-
-
-
-
-
-
-
3
-
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-
-
-
-
-
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10
3
1
2
1
1
-
-
-
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1
-
2
2
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
5252
Scholtz
-
Substrates of hydroxyketogluta ...
Rattus norvegicus
Bioorg. Chem.
12
229-234
1984
-
1
-
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-
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9
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1
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1
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1
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1
2
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3
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1
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9
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1
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1
-
1
2
-
3
-
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-
-
-
-
-
-
-
-
-
-
-
-
-
5250
Grady
Steady-state kinetics and inhi ...
Bos taurus
Biochemistry
20
2497-2502
1981
2
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-
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13
1
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1
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3
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2
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1
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-
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-
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-
2
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-
13
-
1
-
1
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-
-
-
-
2
-
-
1
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-
-
-
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5247
Lane
Sulfhydryl groups in relation ...
Bos taurus
Biochim. Biophys. Acta
481
212-221
1977
-
-
-
-
-
-
2
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-
1
-
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-
2
-
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-
2
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1
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2
-
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1
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-
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2
-
-
1
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-
-
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-
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5246
Hansen
Inactivation of bovine liver 2 ...
Bos taurus
Biochemistry
15
2912-2917
1976
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-
-
-
-
1
1
-
-
1
-
-
-
3
-
-
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-
-
1
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1
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1
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1
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-
1
-
-
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-
-
-
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-
-
-
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-
-
-
-
5243
Dekker
2-keto-4-Hydroxyglutarate aldo ...
Bos taurus
Methods Enzymol.
42C
280-285
1975
-
-
-
-
-
-
1
3
-
1
1
-
-
2
-
-
1
-
-
2
1
1
2
-
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-
-
-
1
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-
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-
1
-
3
-
1
1
-
-
-
-
1
-
2
1
1
2
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
2159
Adams
-
Enzymes and intermediates of h ...
Rattus norvegicus
Methods Enzymol.
17B
266-306
1971
-
-
-
-
-
-
2
2
-
1
1
1
-
1
-
-
1
-
-
1
1
-
4
-
1
-
-
-
-
-
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-
-
-
-
-
-
-
2
-
2
-
1
1
1
-
-
-
1
-
1
1
-
4
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
5238
Lane
2-keto-4-Hydroxybutyrate aldol ...
Bos taurus, Mammalia
Biochemistry
10
1353-1364
1971
-
-
-
-
-
-
4
2
-
2
-
2
-
2
-
-
1
-
-
1
2
-
6
-
1
-
1
-
2
2
-
-
-
-
-
-
-
-
-
-
-
-
-
4
-
2
-
2
-
2
-
-
-
1
-
1
2
-
6
-
1
-
1
-
2
2
-
-
-
-
-
-
-
-
5241
Kobes
Variant properties of bovine l ...
Bos taurus
Biochim. Biophys. Acta
251
238-250
1971
-
-
-
-
-
-
1
-
-
1
-
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2
-
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-
-
2
-
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7
-
-
-
-
1
-
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-
-
-
-
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1
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1
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-
-
-
-
2
-
-
7
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
5237
Kuratomi
The metabolism of gamma-hydrox ...
Rattus norvegicus
Biochim. Biophys. Acta
78
617-628
1963
-
-
-
-
-
-
7
3
1
1
-
-
-
1
-
-
1
-
-
3
1
-
4
-
1
-
-
-
1
1
-
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-
-
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-
-
-
-
-
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7
-
3
1
1
-
-
-
-
-
1
-
3
1
-
4
-
1
-
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1
1
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