Information on EC 4.1.2.52 - 4-hydroxy-2-oxoheptanedioate aldolase

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The expected taxonomic range for this enzyme is: Escherichia coli

EC NUMBER
COMMENTARY hide
4.1.2.52
-
RECOMMENDED NAME
GeneOntology No.
4-hydroxy-2-oxoheptanedioate aldolase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
4-hydroxy-2-oxoheptanedioate = pyruvate + succinate semialdehyde
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
4-hydroxyphenylacetate degradation
-
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Microbial metabolism in diverse environments
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Tyrosine metabolism
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4-hydroxyphenylacetate degradation
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SYSTEMATIC NAME
IUBMB Comments
4-hydroxy-2-oxoheptanedioate succinate semialdehyde lyase (pyruvate-forming)
Requires Co2+ or Mn2+ for activity. The enzyme is also able to catalyse the aldol cleavage of 4-hydroxy-2-oxopentanoate and 4-hydroxy-2-oxohexanoate, and can use 2-oxobutanoate as carbonyl donor, with lower efficiency. In the reverse direction, is able to condense a range of aldehyde acceptors with pyruvate. The enzyme from the bacterium Escherichia coli produces a racemic mixture of (4R)- and (4S)-hydroxy-2-oxoheptanedioate [4].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-4-hydroxy-2-oxopentanoate
?
show the reaction diagram
-
-
-
?
2-oxo-3-methyl-4-hydroxypentanoate
2-oxobutyrate + acetaldehyde
show the reaction diagram
efficient substrate
-
-
?
2-oxobutanoate + acetaldehyde
?
show the reaction diagram
-
-
-
-
?
3-deoxy-D-manno-oct-2-ulosonic acid
?
show the reaction diagram
3-deoxy-D-manno-oct-2-ulosonic acid i.e. KDO
-
-
?
4-hydroxy-2-oxo-heptanedioate
pyruvate + succinic semialdehyde
show the reaction diagram
-
-
-
-
?
4-hydroxy-2-oxoheptane-1,7-dioate
pyruvate + succinate semialdehyde
show the reaction diagram
-
-
-
?
4-hydroxy-2-oxoheptanedioate
pyruvate + succinate semialdehyde
show the reaction diagram
-
-
-
?
4-hydroxy-2-oxohexanoate
?
show the reaction diagram
-
-
-
?
4-hydroxy-2-oxopentanoate
?
show the reaction diagram
-
-
-
?
4-hydroxy-2-oxopentanoic acid
pyruvate + ?
show the reaction diagram
-
-
-
-
?
pyruvate + acetaldehyde
4-hydroxy-2-oxopentanoate
show the reaction diagram
-
-
enzyme lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate i.e. HOPA
-
?
pyruvate + butyraldehyde
?
show the reaction diagram
-
-
-
-
?
pyruvate + DL-glyceraldehyde
?
show the reaction diagram
-
-
-
-
?
pyruvate + glycolaldehyde
?
show the reaction diagram
-
-
-
-
?
pyruvate + isobutyraldehyde
?
show the reaction diagram
-
-
-
-
?
pyruvate + pentaldehyde
?
show the reaction diagram
-
-
-
-
?
pyruvate + propionaldehyde
?
show the reaction diagram
-
-
-
-
?
pyruvate + succinic semialdehyde
4-hydroxy-2-oxo-1,7-heptanedioate
show the reaction diagram
-
-
enzyme lacks stereospecific control producing racemic mixtures of its physiological substrate, 4-hydroxy-2-oxo-1,7-heptanedioate
-
?
additional information
?
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the enzyme exhibits significant oxaloacetate decarboxylase activity, with a kcat value 2.4fold higher than the corresponding value for the aldol cleavage of 4-hydroxy-2-oxopentanoate
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-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
4-hydroxy-2-oxo-heptanedioate
pyruvate + succinic semialdehyde
show the reaction diagram
-
-
-
-
?
4-hydroxy-2-oxoheptane-1,7-dioate
pyruvate + succinate semialdehyde
show the reaction diagram
B1IS70
-
-
-
?
4-hydroxy-2-oxoheptanedioate
pyruvate + succinate semialdehyde
show the reaction diagram
Q47098
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-
-
?
pyruvate + succinic semialdehyde
4-hydroxy-2-oxo-1,7-heptanedioate
show the reaction diagram
-
-
enzyme lacks stereospecific control producing racemic mixtures of its physiological substrate, 4-hydroxy-2-oxo-1,7-heptanedioate
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
-
0.5 mM chloride salt, 4% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Cu2+
-
0.5 mM chloride salt, 1% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Fe2+
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0.5 mM chloride salt, 57% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Mg2+
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0.5 mM chloride salt, 49% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Mn2+
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0.5 mM chloride salt, 99% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Ni2+
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0.5 mM chloride salt, 11% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Zn2+
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0.5 mM chloride salt, 73% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-oxobutanoate
-
competitive inhibition
2-Oxopentanoate
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competitive inhibition
4-methyl-2-oxopentanoate
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competitive inhibition
glyoxylate
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competitive inhibition
pyruvate
sodium oxalate
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-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.38 - 3.32
(S)-4-hydroxy-2-oxopentanoate
0.05
2-oxo-3-methyl-4-hydroxypentanoate
wild type enzyme, at pH 8.0 and 25°C
14.22
3-deoxy-D-manno-oct-2-ulosonic acid
-
i.e. KDO, pH 8.0, 25°C
0.35
4-hydroxy-2-oxoheptane-1,7-dioate
using H2O as solvent, in the presence of 0.5 mM Co2+, at pH 8.0 and 25°C
0.16
4-hydroxy-2-oxohexanoate
-
pH 8.0, 25°C
0.006 - 0.38
4-hydroxy-2-oxopentanoate
0.38 - 38
4-hydroxy-2-oxopentanoic acid
50.1 - 62.9
acetaldehyde
13.4
Butyraldehyde
-
Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
88.6
DL-glyceraldehyde
-
Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
33.3
glycolaldehyde
-
Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
73.8
Isobutyraldehyde
-
Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
32.9
propionaldehyde
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Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
5.6
pyruvate
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steady-state kinetic parameter, pH 8.0 and 25°C
9.1
Succinic semialdehyde
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Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
additional information
additional information
-
apparent Km values for Co2+ increase in the two mutants H45A and H45Q by about 800fold compared to the wild-type enzyme
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
11.8 - 353.5
(S)-4-hydroxy-2-oxopentanoate
14
2-oxo-3-methyl-4-hydroxypentanoate
Escherichia coli
B1IS70
wild type enzyme, at pH 8.0 and 25°C
0.55
3-deoxy-D-manno-oct-2-ulosonic acid
Escherichia coli
-
i.e. KDO, pH 8.0, 25°C
361.5
4-hydroxy-2-oxoheptane-1,7-dioate
Escherichia coli
B1IS70
using H2O as solvent, in the presence of 0.5 mM Co2+, at pH 8.0 and 25°C
229
4-hydroxy-2-oxohexanoate
Escherichia coli
-
pH 8.0, 25°C
353
4-hydroxy-2-oxopentanoate
Escherichia coli
-
pH 8.0, 25°C
0.17 - 350
4-hydroxy-2-oxopentanoic acid
21.9 - 205.4
acetaldehyde
132.5
Butyraldehyde
Escherichia coli
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
5.6
DL-glyceraldehyde
Escherichia coli
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
175.5
glycolaldehyde
Escherichia coli
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
64.9
Isobutyraldehyde
Escherichia coli
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
358.4
propionaldehyde
Escherichia coli
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
219.5
pyruvate
Escherichia coli
-
steady-state kinetic parameter, with acetaldehyde as aldehyde donor, pH 8.0 and 25°C
203.8
Succinic semialdehyde
Escherichia coli
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.55 - 941
(S)-4-hydroxy-2-oxopentanoate
5073
0.03868
3-deoxy-D-manno-oct-2-ulosonic acid
Escherichia coli
-
i.e. KDO, pH 8.0, 25°C
42489
1000
4-hydroxy-2-oxoheptane-1,7-dioate
Escherichia coli
B1IS70
using H2O as solvent, in the presence of 0.5 mM Co2+, at pH 8.0 and 25°C
10416
1460
4-hydroxy-2-oxohexanoate
Escherichia coli
-
pH 8.0, 25°C
2062
940
4-hydroxy-2-oxopentanoate
Escherichia coli
-
pH 8.0, 25°C
1197
0.011 - 930
4-hydroxy-2-oxopentanoic acid
12241
0.4 - 3.3
acetaldehyde
90
9.9
Butyraldehyde
Escherichia coli
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
499
0.063
DL-glyceraldehyde
Escherichia coli
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
487
5.27
glycolaldehyde
Escherichia coli
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
604
0.9
Isobutyraldehyde
Escherichia coli
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
1646
20
pentaldehyde
Escherichia coli
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
3401
10.9
propionaldehyde
Escherichia coli
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
273
22.2
Succinic semialdehyde
Escherichia coli
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
809
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.5
2-oxobutanoate
-
pH 8.0, 25°C
3.6
2-Oxopentanoate
-
pH 8.0, 25°C
6.98
4-methyl-2-oxopentanoate
-
pH 8.0, 25°C
0.4
glyoxylate
-
pH 8.0, 25°C
0.51 - 2.01
pyruvate
0.0055
sodium oxalate
-
pH 8.0, 25°C
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain ATCC 8739 / DSM 1576 / Crooks)
Escherichia coli (strain ATCC 8739 / DSM 1576 / Crooks)
Escherichia coli (strain ATCC 8739 / DSM 1576 / Crooks)
Escherichia coli (strain ATCC 8739 / DSM 1576 / Crooks)
Escherichia coli (strain ATCC 8739 / DSM 1576 / Crooks)
Escherichia coli (strain ATCC 8739 / DSM 1576 / Crooks)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
sizes of the native mutant enzymes are identical to that of the wild-type enzyme as determined by gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
-
6 * 28000
trimer of dimers
x-ray crystallography
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallization of apo-HpcH, because divalent metal ion is lost during the purification process, resulting in preparation of the inactive apo form of the enzyme, crystals grown using the hanging-drop vapour diffusion method; HpcH–Mg2+–oxamate crystals grown with the addition of 10 mM magnesium chloride and sodium oxamate (substrate analogue), elucidation of active site architecture
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in complex with substrate or products, hanging drop vapor diffusion method, using
the active site of HpaI is formed by approx. 30 residues from adjacent dimers and consists of an approx. 15 A deep bell-shaped cleft with an approx. 12 A wide mouth. This broad entrance to the active site is predominantly lined with noncharged residues and a few positively charged residues
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the engineering results show that His45 has a structural and catalytic role. It is important for metal cofactor binding, possibly by proper positioning of a metal cofactor water ligand and is also involved in base catalysis.
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by anion exchange, hydrophobic interaction, and gel filtration chormatography
-
metal affinity and size exclusion chromatography, Superdex 200 column used
-
wild type protein and R70A mutant protein purified to homogeneity using anion exchange, hydrophobic interaction, and gel filtration chormatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HpaI wild type and R70A mutant expressed in Escherichia coli BL21(lambda DE3) under the control of the T7 promoter from expression plasmid pT7-7
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HpcH gene expressed in Escherichia coli strain B834 (DE3)
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mutant HpaI enzymes expressed in Escherichia coli Bl21(lambda DE3) cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D42A
inactive, the mutation leads to a concomitant loss of the metal ion
R70K
the mutation reduces catalytic efficiency by 270fold
Show AA Sequence (440 entries)
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