Information on EC 5.2.1.2 - Maleylacetoacetate isomerase

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

EC NUMBER
COMMENTARY hide
5.2.1.2
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RECOMMENDED NAME
GeneOntology No.
Maleylacetoacetate isomerase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
4-Maleylacetoacetate = 4-fumarylacetoacetate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cis-trans-isomerization
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
L-tyrosine degradation I
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Metabolic pathways
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Microbial metabolism in diverse environments
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Styrene degradation
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Tyrosine metabolism
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tyrosine metabolism
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SYSTEMATIC NAME
IUBMB Comments
4-Maleylacetoacetate cis-trans-isomerase
Also acts on maleylpyruvate.
CAS REGISTRY NUMBER
COMMENTARY hide
9023-75-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SWISSPROT
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
strain CL1
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-
Manually annotated by BRENDA team
strain CL1
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
strain W
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-
Manually annotated by BRENDA team
strain W
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Manually annotated by BRENDA team
strain 01
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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human polymorphisms in the glutathione transferase zeta 1/maleylacetoacetate isomerase gene influence the toxicokinetics of dichloroacetate, GSTz1/MAAI haplotype significantly affects the kinetics and biotransformation of dichloroacetate. GSTz1/MAAI variants associated with the slowest rates of dichlorocacetate metabolism induce structural changes in the enzyme homodimer, predicting protein instability or abnormal protein-protein interactions. Enzyme inhibition also results in the accumulation of the potentially hepatotoxic tyrosine intermediates maleylacetoacetate and maleylacetone and of delta-aminolevulinate
metabolism
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid + glutathione
2-(glutathion-S-yl)-3-(4-nitrophenyl)propanoic acid
show the reaction diagram
4-maleylacetoacetate
4-fumarylacetoacetate
show the reaction diagram
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
show the reaction diagram
chlorofluoroacetic acid + ?
glyoxylate + ?
show the reaction diagram
-
activity assay
-
-
?
cis-beta-Acetylacrylate
trans-beta-Acetylacrylate
show the reaction diagram
Maleylacetoacetate
?
show the reaction diagram
Maleylacetoacetate
Fumarylacetoacetate
show the reaction diagram
Maleylpyruvate
Fumarylpyruvate
show the reaction diagram
Monomethyl 2(Z),4(E)-muconate
Monomethyl 2(E),4(E)-muconate
show the reaction diagram
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+ GSH
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-
Monomethyl 5-oxo-1(E),3(Z)-hexadien-1-ylphosphonate monoanion
Monomethyl 5-oxo-1(Z),3(E)-hexadien-1-ylphosphonate monoanion
show the reaction diagram
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cis-trans double isomerization
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-
additional information
?
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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-maleylacetoacetate
4-fumarylacetoacetate
show the reaction diagram
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-
-
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?
Maleylacetoacetate
?
show the reaction diagram
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Dichloroacetate
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the sensitivity to the inhibitor varies between enzyme haplotypes. Three nonsynonymous single-nucleotide polymorphisms of GSTz1/MAAI show different activity toward dichloroacetate and certain other xenobiotic haloacids
Dichloroacetic acid
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DCA
GSSG
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iodoacetate
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maleylacetone
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inhibits isomerization of 6-oxo-2(E),4(Z)-heptanedienoic acid into 6-oxo-2(Z),4(E)-heptanedienoic acid, and the reverse reaction
N-Hexylmaleamic acid
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noncompetitive towards GSH and maleylacetone
NaBH4
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inhibition in absence of substrate, increases activity in presence of substrate and GSH
S-Glutathioyl-N-hexylmaleamate
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competitive towards GSH, uncompetitive towards maleylacetone
S-Methylglutathione
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.023 - 0.417
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
0.068 - 0.64
4-Maleylacetoacetate
1.9
6-Oxo-2(E),4(Z)-heptanedienoic acid
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3.2
6-Oxo-2(Z),4(E)-heptanedienoic acid
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3
cis-beta-Acetylacrylate
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0.14
GSH
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0.8
maleylacetone
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2.9
trans-beta-Acetylacrylate
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.19 - 6.08
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
2.1 - 464
4-Maleylacetoacetate
additional information
additional information
Vibrio sp.
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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spectrophotometric assay with (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2 - 8
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10.5 - 11
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reaction with (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid and glutathione
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9
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pH 6.0: about 60% of maximal activity, pH 7.2-8.0: maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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GSTzeta/MAAI is induced during the differentiation of 3T3-L1 fibroblasts into adipocytes. This process requires expression of C/EBPalpha as well as PPARgamma
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Anaeromyxobacter dehalogenans (strain 2CP-1 / ATCC BAA-258)
Anaeromyxobacter dehalogenans (strain 2CP-1 / ATCC BAA-258)
Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
33500
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1 * 33500, SDS-PAGE
35000
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gel filtration
36000
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gel filtration
50000
dimer, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
50000, gel filtration
monomer
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1 * 33500, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, 1.9 A resolution
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
10-15 mM mercaptoethanol stabilizes
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
of the recombinant protein
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli, his-tagged protein is mainly insoluble
gene GSTz1/MAAI is located on chromosome 14q24.3, genotyping, overview
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C16A
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the ratio of turnover number to KM-value for (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid is 2.1fold decreased compared to the wild-type enzyme, the ratio of turnover number to KM-value for 4-maleylacetoacetate is 1.6fold increased compared to wild-type enzyme
R175A
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the ratio of turnover number to KM-value for (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid is 1.5fold decreased compared to the wild-type enzyme, the ratio of turnover number to KM-value for 4-maleylacetoacetate is 6.8fold decreased compared to wild-type enzyme
R175K
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the ratio of turnover number to KM-value for (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid is 1.8fold increased compared to the wild-type enzyme, the ratio of turnover number to KM-value for 4-maleylacetoacetate is 1.3fold increased compared to wild-type enzyme
S14A
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mutant enzyme shows no activity with {(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid} or 4-maleylacetoacetate
S15A
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the ratio of turnover number to KM-value for (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid is 2.3fold decreased compared to the wild-type enzyme, the ratio of turnover number to KM-value for 4-maleylacetoacetate is 11.8fold decreased compared to wild-type enzyme
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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cis and/or trans isomers of 2,4-dioxohept-2-enoic acid might be diagnostic for human deficiency of maleylacetoacetate isomerase
additional information
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knowledge of the GSTz1/MAAI haplotype can be used prospectively to identify individuals at potential risk of dichloroacetates adverse side effects from environmental or clinical exposure or who may exhibit aberrant amino acid metabolism in response to dietary protein
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