Information on EC 4.1.3.17 - 4-hydroxy-4-methyl-2-oxoglutarate aldolase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
4.1.3.17
-
RECOMMENDED NAME
GeneOntology No.
4-hydroxy-4-methyl-2-oxoglutarate aldolase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2-hydroxy-4-oxobutane-1,2,4-tricarboxylate = oxaloacetate + pyruvate
show the reaction diagram
(2)
-
-
-
4-hydroxy-4-methyl-2-oxoglutarate = 2 pyruvate
show the reaction diagram
(1)
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
elimination
-
-
of an oxo-acid, C-C bond cleavage
-
PATHWAY
KEGG Link
MetaCyc Link
Benzoate degradation
-
C5-Branched dibasic acid metabolism
-
gallate degradation I
-
gallate degradation II
-
methylgallate degradation
-
Microbial metabolism in diverse environments
-
protocatechuate degradation I (meta-cleavage pathway)
-
SYSTEMATIC NAME
IUBMB Comments
4-hydroxy-4-methyl-2-oxoglutarate pyruvate-lyase (pyruvate-forming)
Requires a divalent metal ion [3]. This enzyme participates in the degradation of protocatechuate (via the meta-cleavage pathway), phthalate, syringate and gallate [1-3]. The enzyme from Pseudomonas ochraceae can also cleave 4-hydroxy-2-oxoglutarate to glyoxylate and pyruvate, and also catalyses the reaction of EC 4.1.1.3 (oxaloacetate decarboxylase) [3].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4-hydroxy-4-methyl-2-ketoglutarate aldolase
-
-
-
-
4-hydroxy-4-methyl-2-oxoglutarate aldolase
-
-
4-hydroxy-4-methyl-2-oxoglutarate aldolase
Pseudomonas straminea NGJ1
-
-
-
aldolase, 4-hydroxy-4-methyl-2-oxoglutarate
-
-
-
-
gamma-methyl-gamma-hydroxy-alpha-ketoglutaric aldolase
-
-
-
-
KDPG aldolase
-
-
MHK aldolase
-
-
-
-
MHKG aldolase
-
-
-
-
pyruvate aldolase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37290-65-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
development of a selection strategy for the evolution of the substrate specificity of KDPG aldolase based on a pyruvate kinase-deficient strain of Escherichia coli
-
-
Manually annotated by BRENDA team
strain NGJ1
-
-
Manually annotated by BRENDA team
Pseudomonas straminea NGJ1
strain NGJ1
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-hydroxy-4-oxopentanedioic acid
?
show the reaction diagram
-
-
-
-
?
4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
-
-
-
-
-
4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
-
-
-
-
4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
-
the L-isomer is preferred, no equilibrium due to oxaloacetate beta-decarboxylase activity associated with the enzyme
-
-
4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
-
L-4-carboxy-4-hydroxy-2-oxoadipate or D-4-carboxy-4-hydroxy-2-oxoadipate
-
-
4-Hydroxy-2-oxoglutarate
Pyruvate + glyoxylate
show the reaction diagram
-
-
-
-
-
4-Hydroxy-2-oxoglutarate
Pyruvate + glyoxylate
show the reaction diagram
-
the L-isomer is preferred
-
-
4-hydroxy-2-oxopentanoate
?
show the reaction diagram
-
-
-
-
?
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate + pyruvate
show the reaction diagram
-
-
-
-
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate + pyruvate
show the reaction diagram
-
-
-
-
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate + pyruvate
show the reaction diagram
-
-
-
-
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate + pyruvate
show the reaction diagram
-
-
-
-
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate + pyruvate
show the reaction diagram
-
-
-
-
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate + pyruvate
show the reaction diagram
-
the L-isomer is preferred
-
-
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate + pyruvate
show the reaction diagram
-
preferentially attacks the R-form of 4-hydroxy-4-methyl-2-oxoglutarate
-
-
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate + pyruvate
show the reaction diagram
-
the enzyme attacks only one enantiomer
-
-
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate
show the reaction diagram
-
involved in biosynthesis of gamma-substituted glutamic acid, participates in the alpha-keto acid pathway for degradation of the meta-fission product of protocatechuate, in Pseudomonas ochraceae grown on phthalate the physiolological substrate is not hydroxymethyl glutamic acid but CHA, L-4-carboxy-4-hydroxy-2-oxoadipate, which is cleaved to pyruvate and oxaloacetate
-
r
4-hydroxy-4-methyl-2-oxoglutarate
2 pyruvate
show the reaction diagram
-
-
-
-
r
D-4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
-
-
-
-
-
D-4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
Pseudomonas straminea, Pseudomonas straminea NGJ1
-
-
-
?
DL-4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
Pseudomonas straminea, Pseudomonas straminea NGJ1
-
-
-
?
DL-4-hydroxy-2-oxoglutarate
pyruvate + glyoxylate
show the reaction diagram
-
-
-
?
DL-4-hydroxy-4-methyl-2-oxoglutarate
pyruvate
show the reaction diagram
Pseudomonas straminea, Pseudomonas straminea NGJ1
-
-
-
?
l-4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
-
-
-
-
-
oxaloacetate
?
show the reaction diagram
-
-
-
-
?
oxaloacetate
?
show the reaction diagram
-
beta-decarboxylation
-
-
-
oxaloacetate
?
show the reaction diagram
Pseudomonas straminea, Pseudomonas straminea NGJ1
-
decarboxylation
-
?
pyruvate + glyoxylate
4-hydroxy-2-oxoglutarate
show the reaction diagram
-
-
-
-
pyruvate + pyruvate
4-hydroxy-4-methyl-2-oxoglutarate
show the reaction diagram
-
-
-
-
pyruvate + pyruvate
4-hydroxy-4-methyl-2-oxoglutarate
show the reaction diagram
-
-
-
-
l-4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
Pseudomonas straminea, Pseudomonas straminea NGJ1
-
-
-
?
additional information
?
-
-
inducible by aromatic carboxylates such as phthalate
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
4-hydroxy-4-methyl-2-oxoglutarate
pyruvate
show the reaction diagram
-
involved in biosynthesis of gamma-substituted glutamic acid, participates in the alpha-keto acid pathway for degradation of the meta-fission product of protocatechuate, in Pseudomonas ochraceae grown on phthalate the physiolological substrate is not hydroxymethyl glutamic acid but CHA, L-4-carboxy-4-hydroxy-2-oxoadipate, which is cleaved to pyruvate and oxaloacetate
-
r
l-4-carboxy-4-hydroxy-2-oxoadipate
pyruvate + oxaloacetate
show the reaction diagram
Pseudomonas straminea, Pseudomonas straminea NGJ1
-
-
-
?
additional information
?
-
-
inducible by aromatic carboxylates such as phthalate
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Cd2+
-
absolute requirement for divalent metal ion: Mg2+, Mn2+, Co2+, Zn2+ or Cd2+; Km: 0.0034 mM, reaction with L-4-carboxy-4-hydroxy-2-oxoadipate
Co2+
-
activates
Co2+
-
absolute requirement for divalent metal ion: Mg2+, Mn2+, Co2+, Zn2+ or Cd2+; Km: 0.0077 mM, reaction with L-4-carboxy-4-hydroxy-2-oxoadipate
Co2+
-
can replace Mg2+
Mg2+
-
required, maximal stimulation with 0.3 mM
Mg2+
-
Km: 0.17 mM MgCl2; Mn2+ or Mg2+ required
Mg2+
-
absolute requirement for divalent metal ion: Mg2+, Mn2+, Co2+, Zn2+ or Cd2+; Km: 0.0323 mM, reaction with L-4-carboxy-4-hydroxy-2-oxoadipate; Km: 0.154 mM, reaction with D-4-carboxy-4-hydroxy-2-oxoadipate
Mg2+
-
virtually no activity in absence of Mg2+ or Pi
Mg2+
-
Mn2+: 90.3% activity, Co2+: 64.7% activity, Zn2+: 49.6% activity
Mn2+
-
Mn2+ or Mg2+ required
Mn2+
-
absolute requirement for divalent metal ion: Mg2+, Mn2+, Co2+, Zn2+ or Cd2+; Km: 0.0059 mM, reaction with L-4-carboxy-4-hydroxy-2-oxoadipate
Zn2+
-
absolute requirement for divalent metal ion: Mg2+, Mn2+, Co2+, Zn2+ or Cd2+, Km: 0.0018 mM, reaction with L-4-carboxy-4-hydroxy-2-oxoadipate
Mn2+
-
can replace Mg2+
additional information
-
metal-requiring aldolase
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-oxoadipate
-
competitive with respect to DL-4-carboxy-4-hydroxy-2-oxoadipate
2-oxobutanoate
-
competitive with respect to DL-4-carboxy-4-hydroxy-2-oxoadipate
2-oxoglutarate
-
competitive with respect to DL-4-carboxy-4-hydroxy-2-oxoadipate
2-oxoglutarate
-
-
4-hydroxy-2-oxobutyrate
-
competitive with respect to DL-4-carboxy-4-hydroxy-2-oxoadipate
citrate
-
competitive
diethyl dicarbonate
-
not reversed by hydroxylamine, L-4-carboxy-4-hydroxy-2-oxoadipate strongly protects against inactivation
DL-4-hydroxy-2-oxovalerate
-
competitive with respect to DL-4-carboxy-4-hydroxy-2-oxoadipate
HgCl2
-
0.1 mM, 41% inhibition
NEM
-
1 mM, 10% inhibition
oxalate
-
competitive inhibitor
oxaloacetate
-
competitive
PCMB
-
1 mM, 48% inhibition
pyruvic aldol lactone
-
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
phosphate
-
activates
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.071
-
2-hydroxy-4-oxopentanedioic acid
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
-
0.15
-
2-hydroxy-4-oxopentanedioic acid
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
-
0.29
-
4-carboxy-4-hydroxy-2-oxoadipate
-
-
8.8
-
4-hydroxy-2-oxopentanoate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
25
-
4-hydroxy-2-oxopentanoate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
0.022
-
4-hydroxy-4-methyl-2-oxoglutarate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
0.067
-
4-hydroxy-4-methyl-2-oxoglutarate
-
-
0.086
-
4-hydroxy-4-methyl-2-oxoglutarate
-
-
0.26
-
4-hydroxy-4-methyl-2-oxoglutarate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
5.5
-
4-hydroxy-4-methyl-2-oxoglutarate
-
R123K mutant protein, pH 8.0, 25C
0.097
-
D-4-carboxy-4-hydroxy-2-oxoadipate
-
activated by Mg2+
0.044
-
DL-4-carboxy-4-hydroxy-2-oxoadipate
-
pH 8.0, 25C
0.24
-
DL-4-hydroxy-2-oxoglutarate
-
pH 8.0, 25C
1.25
-
DL-4-hydroxy-4-methyl-2-oxoglutarate
-
pH 8.0, 25C
0.0065
-
L-4-carboxy-4-hydroxy-2-oxoadipate
-
activated by Zn2+
0.0074
-
L-4-carboxy-4-hydroxy-2-oxoadipate
-
activated by Co2+
0.0075
-
L-4-carboxy-4-hydroxy-2-oxoadipate
-
activated by Cd2+
0.0086
-
L-4-carboxy-4-hydroxy-2-oxoadipate
-
activated by Mn2+
0.0088
-
L-4-carboxy-4-hydroxy-2-oxoadipate
-
activated by Mg2+
0.019
-
L-4-carboxy-4-hydroxy-2-oxoadipate
-
pH 8.0, 25C
0.15
-
L-4-carboxy-4-hydroxy-2-oxoadipate
-
pH 8.0, 25C
0.036
-
oxaloacetate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C; substrate inhibition constante 0.25 mM
0.3
-
oxaloacetate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C; substrate inhibition constante 0.37 mM
0.5
-
oxaloacetate
-
pH 8.0, 25C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.058
-
2-hydroxy-4-oxopentanedioic acid
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
-
0.25
-
2-hydroxy-4-oxopentanedioic acid
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
-
0.048
-
4-hydroxy-2-oxopentanoate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
0.19
-
4-hydroxy-2-oxopentanoate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
0.099
-
4-hydroxy-4-methyl-2-oxoglutarate
-
R123K mutant protein, pH 8.0, 25C
13.7
-
4-hydroxy-4-methyl-2-oxoglutarate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
19.3
-
4-hydroxy-4-methyl-2-oxoglutarate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
1.52
-
oxaloacetate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
1.85
-
oxaloacetate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.38
-
2-hydroxy-4-oxopentanedioic acid
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
0
3.5
-
2-hydroxy-4-oxopentanedioic acid
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
0
0.0019
-
4-hydroxy-2-oxopentanoate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
4524
0.022
-
4-hydroxy-2-oxopentanoate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
4524
74
-
4-hydroxy-4-methyl-2-oxoglutarate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
4539
620
-
4-hydroxy-4-methyl-2-oxoglutarate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
4539
6.2
-
oxaloacetate
-
wild type protein, 1.0 mM Mg2+, pH 8.0, 25C
14857
420
-
oxaloacetate
-
wild type protein, 1.0 mM Mn2+, pH 8.0, 25C
14857
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0017
-
oxalate
-
1 mM MnCl, pH 8.0, 25C
0.005
-
oxalate
-
1 mM MgCl, pH 8.0, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37.7
-
-
wild type protein, pH 8.0, 25C
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.6
-
-
L-4-carboxy-4-hydroxy-2-oxoadipate, without phosphate
7.7
-
-
L-4-carboxy-4-hydroxy-2-oxoadipate, in presence of 0.2 mM phosphate
8
-
-
D-4-carboxy-4-hydroxy-2-oxoadipate, without phosphate
8.2
-
-
L-4-carboxy-4-hydroxy-2-oxoadipate, with 3 mM phosphate
8.3
-
-
DL-4-hydroxy-4-methyl-2-oxoglutarate, without phosphate
8.3
-
-
L-4-carboxy-4-hydroxy-2-oxoadipate, in presence of 0.2 mM phosphate
8.4
-
-
DL-4-hydroxy-4-methyl-2-oxoglutarate, in presence of 0.2 mM phosphate
8.6
-
-
D-4-carboxy-4-hydroxy-2-oxoadipate, with 3 mM phosphate
8.8
-
-
oxaloacetate, without phosphate
8.9
-
-
DL-4-hydroxy-4-methyl-2-oxoglutarate or oxaloacetate, with 3 mM phosphate
8.9
-
-
oxaloacetate
9
-
-
and above
9.4
-
-
DL-4-hydroxy-2-oxoglutarate, in presence of 0.2 mM oxoglutarate
additional information
-
-
broad optimum (log KCAT) pH 8 - pH 10.5
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.5
9.5
-
pH 7.5: about 30% of maximal activity, pH 9.5: about 65% of maximal activity
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
-
isoelectric focusing
5.7
-
-
predicted pI
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
Pseudomonas putida (strain F1 / ATCC 700007)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
24070
-
-
calculated from amino acid sequence corresponding to gene sequence
150000
-
-
equilibrium sedimentation
160000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hexamer
-
6 * 27000, SDS-PAGE
hexamer
-
6 * 26000, SDS-PAGE
hexamer
-
6 * 26000, homohexamer, SDS-PAGE
hexamer
Pseudomonas straminea NGJ1
-
6 * 26000, homohexamer, SDS-PAGE
-
homohexamer
-
6 * 26000, crystal structure, gel filtration and SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hanging drop method, PEG 4000
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
54C, 10 min, 50% loss of activity
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
54
-
-
pH 7.0, 10 min, 50% loss of activity
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, 20 mM sodium HEPES buffer, pH7.5, stable for 2 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ion exchange chromatography, hydrophobic interaction chromatography, gel filtration
-
wild-type and recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli BL21(lambdaDE3)
-
DNA fragment carrying the gene proA from chromosomal DNA cloned and overproduced in Escherichia coli XL1-Blue MRF'
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
R123A
-
no activity
R123K
-
retains some activity