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Information on EC 4.1.2.52 - 4-hydroxy-2-oxoheptanedioate aldolase
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4.1.2.52 4-hydroxy-2-oxoheptanedioate aldolaseIUBMB Comments
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 .
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The expected taxonomic range for this enzyme is: Bacteria, Archaea
Synonyms
4-hydroxy-2-oxo-heptane-1,7-dioate aldolase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
HpaI
HpcH
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4-hydroxy-2-oxoheptanedioate = pyruvate + succinate semialdehyde
-
-
-
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4-hydroxy-2-oxoheptanedioate = pyruvate + succinate semialdehyde
rapid equilibrium random order mechanism
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PATHWAY SOURCE
PATHWAYS
-
-
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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].
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-oxo-3-methyl-4-hydroxypentanoate
2-oxobutyrate + acetaldehyde
efficient substrate
-
-
?
3-deoxy-D-manno-oct-2-ulosonic acid
?
3-deoxy-D-manno-oct-2-ulosonic acid i.e. KDO
-
-
?
4-hydroxy-2-oxoheptane-1,7-dioate
pyruvate + succinate semialdehyde
-
-
-
?
4-hydroxy-2-oxoheptanedioate
pyruvate + succinate semialdehyde
-
-
-
?
pyruvate + acetaldehyde
4-hydroxy-2-oxopentanoate
-
-
enzyme lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate i.e. HOPA
-
?
pyruvate + succinic semialdehyde
4-hydroxy-2-oxo-1,7-heptanedioate
-
-
enzyme lacks stereospecific control producing racemic mixtures of its physiological substrate, 4-hydroxy-2-oxo-1,7-heptanedioate
-
?
additional information
?
-
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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-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-hydroxy-2-oxoheptane-1,7-dioate
pyruvate + succinate semialdehyde
-
-
-
?
4-hydroxy-2-oxoheptanedioate
pyruvate + succinate semialdehyde
-
-
-
?
pyruvate + succinic semialdehyde
4-hydroxy-2-oxo-1,7-heptanedioate
-
-
enzyme lacks stereospecific control producing racemic mixtures of its physiological substrate, 4-hydroxy-2-oxo-1,7-heptanedioate
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cd2+
0.5 mM chloride salt, 4% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Co2+
Cu2+
0.5 mM chloride salt, 1% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Fe2+
0.5 mM chloride salt, 57% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Mg2+
0.5 mM chloride salt, 49% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Mn2+
0.5 mM chloride salt, 99% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Ni2+
0.5 mM chloride salt, 11% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
Zn2+
0.5 mM chloride salt, 73% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
additional information
Co2+
0.5 mM chloride salt, 100% relative activity, with 4-hydroxy-2-oxopentanoate as substrate
additional information
H45A and H45Q mutant enzymes have 24fold and 69fold higher dissociation constants for Co2+ compared to the wild-type enzyme
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
2-oxo-3-methyl-4-hydroxypentanoate
wild type enzyme, at pH 8.0 and 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
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
-
Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
9.1
Succinic semialdehyde
-
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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0.38
(S)-4-hydroxy-2-oxopentanoate
wild type enzyme, with 0.5 mM Co2+, at pH 8.0 and 25°C
3.32
(S)-4-hydroxy-2-oxopentanoate
mutant enzyme R70K, with 0.5 mM Co2+, at pH 8.0 and 25°C
50.1
acetaldehyde
-
Km(app) with 2-oxobutanoate as carbonyl donor, pH 8.0 and 25°C
62.9
acetaldehyde
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Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14
2-oxo-3-methyl-4-hydroxypentanoate
wild type enzyme, at pH 8.0 and 25°C
361.5
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
132.5
Butyraldehyde
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
5.6
DL-glyceraldehyde
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
175.5
glycolaldehyde
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
64.9
Isobutyraldehyde
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
358.4
propionaldehyde
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
219.5
pyruvate
-
steady-state kinetic parameter, with acetaldehyde as aldehyde donor, pH 8.0 and 25°C
203.8
Succinic semialdehyde
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
11.8
(S)-4-hydroxy-2-oxopentanoate
mutant enzyme R70K, with 0.5 mM Co2+, at pH 8.0 and 25°C
353.5
(S)-4-hydroxy-2-oxopentanoate
wild type enzyme, with 0.5 mM Co2+, at pH 8.0 and 25°C
21.9
acetaldehyde
-
Kcat(app) with 2-oxobutanoate as carbonyl donor, pH 8.0 and 25°C
205.4
acetaldehyde
-
Kcat(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1000
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
9.9
Butyraldehyde
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
0.063
DL-glyceraldehyde
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
5.27
glycolaldehyde
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
0.9
Isobutyraldehyde
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
20
pentaldehyde
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
10.9
propionaldehyde
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
22.2
Succinic semialdehyde
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
3.55
(S)-4-hydroxy-2-oxopentanoate
mutant enzyme R70K, with 0.5 mM Co2+, at pH 8.0 and 25°C
941
(S)-4-hydroxy-2-oxopentanoate
wild type enzyme, with 0.5 mM Co2+, at pH 8.0 and 25°C
0.4
acetaldehyde
-
Kcat/Km(app) with 2-oxobutanoate as carbonyl donor, pH 8.0 and 25°C
3.3
acetaldehyde
-
Kcat/Km(app) with pyruvate as carbonyl donor, pH 8.0 and 25°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
metabolism
enzyme is involved in the catabolic pathway of hydroxyphenylacetate
Show AA Sequence and Transmembrane Helices (2354 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
28000
additional information
sizes of the native mutant enzymes are identical to that of the wild-type enzyme as determined by gel filtration
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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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
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HpcHMg2+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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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D42A
inactive, the mutation leads to a concomitant loss of the metal ion
H45A
H45Q
R70A
H45A
by site-directed mutagenesis, mutant enzyme has 24fold higher dissociation constant for Co2+ compared to the wild-type enzyme, apparent Km value for Co2+ increases by about 800fold compared to the wild-type enzyme, different kcat and km values
H45A
the mutation leads to a decrease in kcat of the enzyme by 78fold
H45Q
by site-directed mutagenesis, mutant enzyme has 69fold higher dissociation constant for Co2+ compared to the wild-type enzyme, apparent Km value for Co2+ increases by about 800fold compared to the wild-type enzyme, different kcat and km values
H45Q
the mutation leads to a decrease in kcat of the enzyme by 2059fold
R70A
replacement by site-specific mutagenesis results in an enzyme that lacks both aldolase and decarboxylase activities. The mutant enzyme is also unable to catalyze pyruvate proton exchange
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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
mutant HpaI enzymes expressed in Escherichia coli Bl21(lambda DE3) cells
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wang, W.; Baker, P.; Seah, S.Y.
Comparison of two metal-dependent pyruvate aldolases related by convergent evolution: substrate specificity, kinetic mechanism, and substrate channeling
Biochemistry
49
3774-3782
2010
Escherichia coli
brenda
Wang, W.; Seah, S.Y.
Purification and biochemical characterization of a pyruvate-specific class II aldolase, HpaI
Biochemistry
44
9447-9455
2005
Escherichia coli (Q47098)
brenda
Wang, W.; Seah, S.Y.
The role of a conserved histidine residue in a pyruvate-specific class II aldolase
FEBS Lett.
582
3385-3388
2008
Escherichia coli (Q47098)
brenda
Rea, D.; Fulop, V.; Bugg, T.D.; Roper, D.I.
Structure and mechanism of HpcH: a metal ion dependent class II aldolase from the homoprotocatechuate degradation pathway of Escherichia coli
J. Mol. Biol.
373
866-876
2007
Escherichia coli
brenda
Coincon, M.; Wang, W.; Sygusch, J.; Seah, S.Y.
Crystal structure of reaction intermediates in pyruvate class II aldolase: substrate cleavage, enolate stabilization, and substrate specificity
J. Biol. Chem.
287
36208-36221
2012
Escherichia coli (B1IS70)
brenda
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Release 2023.1 (January 2023)
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