BRENDA - Enzyme Database
show all sequences of 4.1.3.16

4-Hydroxy-2-oxoglutarate aldolase inactivity in primary hyperoxaluria type 3 and glyoxylate reductase inhibition

Riedel, T.J.; Knight, J.; Murray, M.S.; Milliner, D.S.; Holmes, R.P.; Lowther, W.T.; Biochim. Biophys. Acta 1822, 1544-1552 (2012)

Data extracted from this reference:

Application
Application
Commentary
Organism
medicine
mutations in the gene encoding for 4-hydroxy-2-oxoglutarate aldolase are associated with an excessive production of oxalate in Primary Hyperoxaluria type 3, PH3. Analysis of nine PH3 human variants reveals that all nine PH3 variants are quite unstable, have a tendency to aggregate, and retain no measurable activity. A buildup of 4-hydroxy-2-oxoglutarate takes place in the urine, sera and liver samples from PH3 patients. One hypothetical component of the molecular basis for the excessive oxalate production in PH3 appears to be the inhibition of glyoxylate reductase by 4-hydroxy-2-oxoglutarate, resulting in a phenotype similar to Primary Hyperoxaluria type 2
Homo sapiens
Cloned(Commentary)
Commentary
Organism
expression in Escherichia coli
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
C257G
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
DeltaE315
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
G287V
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
P190L
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
R255X
a truncation of 71 residues from the C-terminus associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
R303C
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
R70P
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
R97C
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
T280I
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
Molecular Weight [Da]
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
35249
-
4 * 35249, calculated
Homo sapiens
131500
-
gel filtration
Homo sapiens
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
Q86XE5
-
-
Specific Activity [micromol/min/mg]
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
15.8
-
pH 8.5, 37°C
Homo sapiens
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4-Hydroxy-2-oxoglutarate
-
721727
Homo sapiens
Pyruvate + glyoxylate
-
-
-
r
Subunits
Subunits
Commentary
Organism
tetramer
4 * 35249, calculated
Homo sapiens
Application (protein specific)
Application
Commentary
Organism
medicine
mutations in the gene encoding for 4-hydroxy-2-oxoglutarate aldolase are associated with an excessive production of oxalate in Primary Hyperoxaluria type 3, PH3. Analysis of nine PH3 human variants reveals that all nine PH3 variants are quite unstable, have a tendency to aggregate, and retain no measurable activity. A buildup of 4-hydroxy-2-oxoglutarate takes place in the urine, sera and liver samples from PH3 patients. One hypothetical component of the molecular basis for the excessive oxalate production in PH3 appears to be the inhibition of glyoxylate reductase by 4-hydroxy-2-oxoglutarate, resulting in a phenotype similar to Primary Hyperoxaluria type 2
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
expression in Escherichia coli
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
C257G
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
DeltaE315
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
G287V
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
P190L
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
R255X
a truncation of 71 residues from the C-terminus associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
R303C
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
R70P
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
R97C
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
T280I
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Homo sapiens
Molecular Weight [Da] (protein specific)
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
35249
-
4 * 35249, calculated
Homo sapiens
131500
-
gel filtration
Homo sapiens
Specific Activity [micromol/min/mg] (protein specific)
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
15.8
-
pH 8.5, 37°C
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
-
721727
Homo sapiens
Pyruvate + glyoxylate
-
-
-
r
Subunits (protein specific)
Subunits
Commentary
Organism
tetramer
4 * 35249, calculated
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 ...
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Appl. Microbiol. Biotechnol.
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HOGA1 gene mutations of prima ...
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747772
MacDonald
Cellular degradation of 4-hyd ...
Homo sapiens
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Huang
Use of a novel microtitration ...
Bos taurus
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721727
Riedel
4-Hydroxy-2-oxoglutarate aldol ...
Homo sapiens
Biochim. Biophys. Acta
1822
1544-1552
2012
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1
1
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9
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2
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4
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1
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1
1
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9
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1
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1
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728378
Williams
The enzyme 4-hydroxy-2-oxoglut ...
Homo sapiens
Nephrol. Dial. Transplant.
27
3191-3195
2012
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1
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723542
Riedel
Structural and biochemical stu ...
Homo sapiens
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2
2
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10
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10
10
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Belostotsky
Mutations in DHDPSL are respon ...
Homo sapiens
Am. J. Hum. Genet.
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392-399
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1
1
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5255
Dekker
2-keto-4-Hydroxyglutarate aldo ...
Bos taurus
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1992
1
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2
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4
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5
1
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7
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1
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5
1
3
5
1
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1
2
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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
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2
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1
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3
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10
3
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1
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2
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1
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5252
Scholtz
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Substrates of hydroxyketogluta ...
Rattus norvegicus
Bioorg. Chem.
12
229-234
1984
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1
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9
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5250
Grady
Steady-state kinetics and inhi ...
Bos taurus
Biochemistry
20
2497-2502
1981
2
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13
1
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1
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3
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13
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1
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5247
Lane
Sulfhydryl groups in relation ...
Bos taurus
Biochim. Biophys. Acta
481
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1977
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2
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1
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5246
Hansen
Inactivation of bovine liver 2 ...
Bos taurus
Biochemistry
15
2912-2917
1976
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1
1
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1
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3
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5243
Dekker
2-keto-4-Hydroxyglutarate aldo ...
Bos taurus
Methods Enzymol.
42C
280-285
1975
-
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1
3
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1
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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2159
Adams
-
Enzymes and intermediates of h ...
Rattus norvegicus
Methods Enzymol.
17B
266-306
1971
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2
2
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1
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5238
Lane
2-keto-4-Hydroxybutyrate aldol ...
Bos taurus, Mammalia
Biochemistry
10
1353-1364
1971
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4
2
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2
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2
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2
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6
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1
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1
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2
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4
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2
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6
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1
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1
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2
2
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5241
Kobes
Variant properties of bovine l ...
Bos taurus
Biochim. Biophys. Acta
251
238-250
1971
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1
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1
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7
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1
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7
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1
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5237
Kuratomi
The metabolism of gamma-hydrox ...
Rattus norvegicus
Biochim. Biophys. Acta
78
617-628
1963
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7
3
1
1
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1
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1
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3
1
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4
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1
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1
1
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7
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1
1
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1
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