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Information on EC 5.2.1.2 - maleylacetoacetate isomerase
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5.2.1.2 maleylacetoacetate isomeraseIUBMB Comments
Also acts on maleylpyruvate.
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Word Map
- 5.2.1.2
- dichloroacetate
- fumarylacetoacetate
-
dca-induced
- succinylacetone
- homogentisate
- tyrosinemia
-
chlorofluoroacetic
- medicine
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
AtGSTZ1, AtMAAI, glutathione S-transferase Zeta 1-1, glutathione S-transferase zeta-class 1, glutathione S-transferase zeta/maleylacetoacetate isomerase, glutathione transferase zeta, glutathione transferase zeta 1/maleylacetoacetate isomerase, Gstz1, GSTZ1-1, GSTz1/MAAI, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GSTZ1-1
Isomerase, maleylacetoacetate
-
-
-
-
MAAI
MAc-tI
-
-
-
-
maleylacetoacetate isomerase
Maleylacetoacetic isomerase
-
-
-
-
Maleylacetone cis-trans-isomerase
-
-
-
-
Maleylacetone isomerase
-
-
-
-
additional information
glutathione transferase zeta 1, EC 2.5.1.18, bifunctional enzyme
MAAI
-
-
-
-
maleylacetoacetate isomerase
-
bifunctional enzyme EC 2.5.1.18, glutathione transferase Zeta, GSTZ1-1
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4-Maleylacetoacetate = 4-fumarylacetoacetate
ordered sequence of binding: maleylacetone first followed by glutathione
-
4-Maleylacetoacetate = 4-fumarylacetoacetate
mechanism, preferred binding order is maleylacetone followed by glutathione
-
4-Maleylacetoacetate = 4-fumarylacetoacetate
tyrosine degradation leads to the formation of homogentisate, maleylacetoacetate isomerase, homogentisate dioxygenase and fumarylacetoacetate hydrolase are expressed in Arabidopsis thaliana to generate fumarate and acetoacetate
4-Maleylacetoacetate = 4-fumarylacetoacetate
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cis-trans-isomerization
cis-trans-isomerization
-
-
double bond
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
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SYSTEMATIC NAME
IUBMB Comments
4-maleylacetoacetate cis-trans-isomerase
Also acts on maleylpyruvate.
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CAS REGISTRY NUMBER
COMMENTARY
9023-75-0
-
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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-bromo-3-(4-nitrophenyl)propionic acid + glutathione
2-(glutathion-S-yl)-3-(4-nitrophenyl)propanoic acid
Monomethyl 5-oxo-1(E),3(Z)-hexadien-1-ylphosphonate monoanion
Monomethyl 5-oxo-1(Z),3(E)-hexadien-1-ylphosphonate monoanion
-
cis-trans double isomerization
-
?
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid + glutathione
2-(glutathion-S-yl)-3-(4-nitrophenyl)propanoic acid
-
it is proposed that the charged side chain of Arg-175 forms a salt bridge with the carboxylate of the alpha-halo acid substrates
-
?
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid + glutathione
2-(glutathion-S-yl)-3-(4-nitrophenyl)propanoic acid
-
-
-
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
-
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
cis-trans double isomerization
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
r, reverse reaction is catalyzed in presence of GSH
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
cis-trans double isomerization
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
r, reverse reaction is catalyzed in presence of GSH
-
?
Maleylacetoacetate
?
human maleylacetoacetate isomerase deficiency presumably causes tyrosinemia that can be characterized by the absence of succinylacetone
-
-
?
Maleylacetoacetate
?
-
enzymatic isomerization of cis,cis-muconaldehydic acid to trans,trans-muconaldehydic acid followed by the oxidation is suggested to be the path to trans,trans-muconate
-
-
?
Maleylacetoacetate
?
-
one of the enzymes responsible for the oxidative metabolism of aromatic amino acids
-
-
?
Maleylpyruvate
Fumarylpyruvate
-
about 20fold higher activity than with maleylacetoacetate
-
?
additional information
?
-
-
enzyme deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone
-
?
additional information
?
-
enzyme deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone
-
?
additional information
?
-
key enzyme in the metabolic degradation of phenylalanine and tyrosine
-
?
additional information
?
-
-
key enzyme in the metabolic degradation of phenylalanine and tyrosine
-
?
additional information
?
-
-
the enzyme plays an important role in the metabolism of tyrosine
-
?
additional information
?
-
-
the bifunctional enzyme dehalogenates dichloroacetate to glyoxalate via its zeta-1 family glutathione transferase activity. Dichloroacetate is relevant to environmental science and allopathic medicine. 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
-
-
?
additional information
?
-
-
GSTzeta/MAAI is induced during the differentiation of 3T3-L1 fibroblasts into adipocytes. This process requires expression of C/EBPalpha as well as PPARgamma
-
-
?
additional information
?
-
-
the enzyme catalyzes the penultimate step in catabolic pathways for phenylalanine and tyrosine. BABL/c GSTZ1/MAAI-deficient mice show a number of significant abnormalities including altered organ sizes, an abnormal pattern of circulating leukocytes, and the consitutive induction of hepatic alpha, mu and pi class glutathione transferases
-
-
?
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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
Maleylacetoacetate
?
human maleylacetoacetate isomerase deficiency presumably causes tyrosinemia that can be characterized by the absence of succinylacetone
-
-
?
Maleylacetoacetate
?
-
enzymatic isomerization of cis,cis-muconaldehydic acid to trans,trans-muconaldehydic acid followed by the oxidation is suggested to be the path to trans,trans-muconate
-
-
?
Maleylacetoacetate
?
-
one of the enzymes responsible for the oxidative metabolism of aromatic amino acids
-
-
?
additional information
?
-
-
enzyme deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone
-
?
additional information
?
-
enzyme deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone
-
?
additional information
?
-
key enzyme in the metabolic degradation of phenylalanine and tyrosine
-
?
additional information
?
-
-
key enzyme in the metabolic degradation of phenylalanine and tyrosine
-
?
additional information
?
-
-
the enzyme plays an important role in the metabolism of tyrosine
-
?
additional information
?
-
-
GSTzeta/MAAI is induced during the differentiation of 3T3-L1 fibroblasts into adipocytes. This process requires expression of C/EBPalpha as well as PPARgamma
-
-
?
additional information
?
-
-
the enzyme catalyzes the penultimate step in catabolic pathways for phenylalanine and tyrosine. BABL/c GSTZ1/MAAI-deficient mice show a number of significant abnormalities including altered organ sizes, an abnormal pattern of circulating leukocytes, and the consitutive induction of hepatic alpha, mu and pi class glutathione transferases
-
-
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3Z)-1,3-butadiene-1,1,2,4-tetrol
competitive inhibitor identified by rational design, calculated to be no substrate and not inhibitory to CYP450 and nontoxic in AMES test
(Z)-3-[4-hydroxy-1-(hydroxymethyl)cyclohexyl]-2-propene-1,2-diol
competitive inhibitor identified by rational design, calculated to be no substrate and not inhibitory to CYP450 and nontoxic in AMES test
Dichloroacetate
-
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
maleylacetone
-
inhibits isomerization of 6-oxo-2(E),4(Z)-heptanedienoic acid into 6-oxo-2(Z),4(E)-heptanedienoic acid, and the reverse reaction
NaBH4
-
inhibition in absence of substrate, increases activity in presence of substrate and GSH
S-Glutathioyl-N-hexylmaleamate
-
competitive towards GSH, uncompetitive towards maleylacetone
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Acidosis, Lactic
Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways.
Acidosis, Lactic
Perturbation of maleylacetoacetic acid metabolism in rats with dichloroacetic Acid-induced glutathione transferase zeta deficiency.
Acidosis, Lactic
Prenatal and postnatal expression of glutathione transferase ? 1 in human liver and the roles of haplotype and subject age in determining activity with dichloroacetate.
Breast Neoplasms
Investigation of glutathione S-transferase zeta and the development of sporadic breast cancer.
Breast Neoplasms
No evidence for glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 in breast cancer risk.
Carcinogenesis
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
Carcinoma, Hepatocellular
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
Carcinoma, Hepatocellular
GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate.
Carcinoma, Hepatocellular
GSTZ1-1 downregulates Wnt/?-catenin signalling in hepatocellular carcinoma cells.
Hematologic Neoplasms
GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial.
Liver Failure
Gene structure, chromosomal location, and expression pattern of maleylacetoacetate isomerase.
Lung Neoplasms
Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis.
Macular Degeneration
Susceptibility to exudative age-related macular degeneration and three genetic polymorphisms of glutathione S-transferase Z1 (GSTZ1).
maleylacetoacetate isomerase deficiency
Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways.
maleylacetoacetate isomerase deficiency
Dichloroacetic acid up-regulates hepatic glutathione synthesis via the induction of glutamate-cysteine ligase.
maleylacetoacetate isomerase deficiency
Exposure of Rats to Multiple Oral Doses of Dichloroacetate Results in Upregulation of Hepatic GSTs and NQO1.
maleylacetoacetate isomerase deficiency
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
maleylacetoacetate isomerase deficiency
GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.
maleylacetoacetate isomerase deficiency
Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate isomerase deficiency.
maleylacetoacetate isomerase deficiency
Oncometabolite modification of Keap1 links GSTZ1 deficiency with cancer.
maleylacetoacetate isomerase deficiency
Perturbation of maleylacetoacetic acid metabolism in rats with dichloroacetic Acid-induced glutathione transferase zeta deficiency.
maleylacetoacetate isomerase deficiency
Phenylalanine-induced leucopenia in genetic and dichloroacetic acid generated deficiency of glutathione transferase Zeta.
Multiple Myeloma
GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial.
Neoplasms
Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate.
Neoplasms
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
Neoplasms
GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate.
Neoplasms
GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.
Neoplasms
GSTZ1-1 downregulates Wnt/?-catenin signalling in hepatocellular carcinoma cells.
Neoplasms
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.
Neoplasms
Prenatal and postnatal expression of glutathione transferase ? 1 in human liver and the roles of haplotype and subject age in determining activity with dichloroacetate.
Neuroblastoma
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.
Ovarian Neoplasms
A panel of three oxidative stress-related genes predicts overall survival in ovarian cancer patients received platinum-based chemotherapy.
Stomach Neoplasms
Glutathione S-transferase Z1 (GSTZ1) gene polymorphism in gastric cancer: a preliminary study in a Turkish population.
Tyrosinemias
Gene structure, chromosomal location, and expression pattern of maleylacetoacetate isomerase.
Urinary Bladder Neoplasms
A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire.
Urinary Bladder Neoplasms
Genotoxicity of disinfection byproducts and disinfected waters: A review of recent literature.
Urinary Bladder Neoplasms
Polymorphisms in GSTT1, GSTZ1, and CYP2E1, Disinfection Byproducts, and Risk of Bladder Cancer in Spain.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.023
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175A
0.027
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175K
0.029
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1d-1d
0.044
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1c-1c
0.096
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1b-1b
0.128
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1a-1a
0.319
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme S15A
0.417
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme C16A
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.19
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175A
0.55
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1d-1d
0.59
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1c-1c
0.61
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175K
0.82
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1b-1b
1
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme S15A
1.3
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1a-1a
2.55
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme C16A
6.08
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1b-1b
6.08
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1c-1c
6.08
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175K
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
spectrophotometric assay with (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10.5 - 11
-
reaction with (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid and glutathione
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional enzyme, catalyzes reactions of EC 5.2.1.2 and glutathione-conjugating activity, EC 2.5.1.18
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
GSTzeta/MAAI is induced during the differentiation of 3T3-L1 fibroblasts into adipocytes. This process requires expression of C/EBPalpha as well as PPARgamma
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
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
metabolism
-
catalyses a significant step in the catabolism of phenylalanine and tyrosine
metabolism
-
the bifunctional enzyme glutathione transferase zeta/maleylacetoacetate isomerase is the penultimate enzyme in the phenylalanine/tyrosine catabolic pathway
Show AA Sequence and Transmembrane Helices (4791 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
16000
16000
-
x * 16000, SDS-PAGE after heating the enzyme at 100°C for 10 min in a standard aqueous medium containing 1% SDS and 8M urea
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 16000, SDS-PAGE after heating the enzyme at 100°C for 10 min in a standard aqueous medium containing 1% SDS and 8M urea
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to 3.1 A resolution, space group P1, with unit-cell parameters a = 42.0, b= 49.6, c = 54.6 A, alpha = 82.9°, beta = 69.9°, gamma = 73.4°
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C16A
-
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
-
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
-
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
-
mutant enzyme shows no activity with {(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid} or 4-maleylacetoacetate
S15A
-
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
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli, his-tagged protein is mainly insoluble
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
additional information
-
knowledge of the GSTz1/MAAI haplotype can be used prospectively to identify individuals at potential risk of dichloroacetate’s adverse side effects from environmental or clinical exposure or who may exhibit aberrant amino acid metabolism in response to dietary protein
medicine
cis and/or trans isomers of 2,4-dioxohept-2-enoic acid might be diagnostic for human deficiency of maleylacetoacetate isomerase
medicine
dichloroacetate, a degradation product of chloral hydrate, is further metabolized by glutathione transferase zeta 1, and inhibits its own metabolism through depletion/inactivation of GSTZ1/MAAI with repeated exposure, resulting in lower plasma clearance of the drug and the accumulation of the urinary biomarker maleylacetone. The amount of dichloroacetate produced from clinically relevant doses of chloral hydrate, although insufficient to alter dichloroacetate kinetics, is sufficient to inhibit MAAI and tyrosine catabolism
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Seltzer, S.
cis-trans Isomerization
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
6
381-406
1972
Vibrio sp.
-
brenda
Hagedorn, S.R.; Chapman, P.J.
Glutathione-independent maleylacetoacetate isomerase in gram-positive bacteria
J. Bacteriol.
163
803-805
1985
Corynebacterium sp., Moraxella sp., Nocardia globerula, Rhodococcus rhodnii, Pseudomonas alcaligenes, Nocardia globerula CL1
brenda
Feliu, A.L.; Smith, K.J.; Seltzer, S.
Unique, one-step, double isomerization (2E,4Z<-->2Z,4E) of 6-oxo-2,4-heptadienoic acid catalyzed by maleylacetone cis-trans isomerase
J. Am. Chem. Soc.
106
3046-3047
1984
Vibrio sp., Vibrio sp. 1
-
brenda
Lin, M.; Seltzer, S.
Maleylacetone cis-trans isomerase: formation of an N-ethylmaleimide-labeled enzyme only during the slow phase of the biphasic inhibition reaction
FEBS Lett.
124
169-172
1981
Vibrio sp.
-
brenda
Seltzer, S.; Lin, M.
Maleylacetone cis-trans-Isomerase. Mechanism of the interaction of coenzyme glutathione and substrate maleylacetone in the presence and absence of enzyme
J. Am. Chem. Soc.
101
3091-3097
1979
Vibrio sp.
-
brenda
Morrison, W.S.; Wong, G.; Seltzer, S.
Maleylacetone cis-trans-isomerase: affinity chromatography on glutathione-bound Sepharose. Two-substrate-binding sequence from inhibition patterns
Biochemistry
15
4228-4233
1976
Vibrio sp.
brenda
Seltzer, S.
Purification and properties of maleylacetone cis-trans isomerase from Vibrio 01
J. Biol. Chem.
248
215-222
1973
Vibrio sp.
brenda
Whitlow, K.J.; D'Iorio, A.; Mavrides, C.
Regulation of the enzymes of tyrosine catabolism in Tetrahymena pyriformis
Biochim. Biophys. Acta
264
440-449
1972
Tetrahymena pyriformis, Tetrahymena pyriformis W
brenda
Lack, L.
Enzymic cis-trans isomerization of maleylpyruvic acid
J. Biol. Chem.
236
2835-2840
1961
Pseudomonas sp.
brenda
Fernandez-Canon, J.M.; Penalva, M.A.
Characterization of a fungal maleylacetoacetate isomerase gene and identification of its human homologue
J. Biol. Chem.
273
329-337
1998
Aspergillus nidulans, Aspergillus nidulans (O43123), Homo sapiens, Homo sapiens (O43708)
brenda
Seltzer, S.; Hane, J.
Maleylacetate cis-trans isomerase: one-step double cis-trans isomerization of monomethyl muconate and the enzyme's probable role in benzene metabolism
Bioorg. Chem.
16
394-407
1988
Vibrio sp.
-
brenda
Angaw-Duguma, L.; Marecek, J.; Seltzer, S.
The synthesis and enzyme-catalyzed one-step cis-trans double isomerization of monomethyl 5-oxo-1,3-hexadien-1-ylphosphonate, an analogue of maleylacetone
Bioorg. Chem.
20
213-222
1992
Vibrio sp.
-
brenda
Seltzer, S.
Maleylacetoacetate cis-trans isomerase
Coenzymes and cofactors, Glutathione, Chem. Biochem. Med. Aspects Pt. A (Dolphin D, Poulson R, Avromonic O, eds. ) John Wiley & Sons, New York
3
733-751
1989
Mammalia, Vibrio sp.
-
brenda
Lee, H.E.; Seltzer, S.
cis-beta-Acetylacrylate is a substrate for maleylacetoacetate cis-trans isomerase. Mechanistic implications
Biochem. Int.
18
91-97
1989
Vibrio sp.
brenda
Board, P.G.; Taylor, M.C.; Coggan, M.; Parker, M.W.; Lantum, H.B.; Anders, M.W.
Clarification of the role of key active site residues of glutathione transferase zeta/maleylacetoacetate isomerase by a new spectrophotometric technique
Biochem. J.
374
731-737
2003
Homo sapiens
brenda
Polekhina, G.; Board, P.G.; Blackburn, A.C.; Parker, M.W.
Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity
Biochemistry
40
1567-1576
2001
Homo sapiens (O43708), Homo sapiens
brenda
Lim, C.E.; Matthaei, K.I.; Blackburn, A.C.; Davis, R.P.; Dahlstrom, J.E.; Koina, M.E.; Anders, M.W.; Board, P.G.
Mice deficient in glutathione transferase zeta/maleylacetoacetate isomerase exhibit a range of pathological changes and elevated expression of alpha, mu, and pi class glutathione transferases
Am. J. Pathol.
165
679-693
2004
Mus musculus
brenda
Qiang, L.; Farmer, S.R.
C/EBPalpha-dependent induction of glutathione S-transferase zeta/maleylacetoacetate isomerase (GSTzeta/MAAI) expression during the differentiation of mouse fibroblasts into adipocytes
Biochem. Biophys. Res. Commun.
340
845-851
2006
Mus musculus
brenda
Dixon, D.P.; Edwards, R.
Enzymes of tyrosine catabolism in Arabidopsis thaliana
Plant Sci.
171
360-366
2006
Arabidopsis thaliana (Q9ZVQ3), Arabidopsis thaliana
brenda
Theodoratos, A.; Tu, W.J.; Cappello, J.; Blackburn, A.C.; Matthaei, K.; Board, P.G.
Phenylalanine-induced leucopenia in genetic and dichloroacetic acid generated deficiency of glutathione transferase Zeta
Biochem. Pharmacol.
77
1358-1363
2009
Mus musculus
brenda
Shroads, A.L.; Langaee, T.; Coats, B.S.; Kurtz, T.L.; Bullock, J.R.; Weithorn, D.; Gong, Y.; Wagner, D.A.; Ostrov, D.A.; Johnson, J.A.; Stacpoole, P.W.
Human polymorphisms in the glutathione transferase zeta 1/maleylacetoacetate isomerase gene influence the toxicokinetics of dichloroacetate
J. Clin. Pharmacol.
52
837-849
2012
Homo sapiens
brenda
Boone, C.; Zhong, G.; Smeltz, M.; James, M.; McKenna, R.
Preliminary X-ray crystallographic analysis of glutathione transferase zeta 1 (GSTZ1a-1a)
Acta Crystallogr. Sect. F
70
187-189
2014
Homo sapiens (O43708)
brenda
Zolfaghari, N.
Competitive rational inhibitor design to 4-maleylaceto-acetate isomerase
Bioinformation
13
140-143
2017
Homo sapiens (O43708)
brenda
Shroads, A.L.; Coats, B.S.; Langaee, T.; Shuster, J.J.; Stacpoole, P.W.
Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans
Drug Metab. Pers. Ther.
30
49-55
2015
Homo sapiens (O43708), Homo sapiens
brenda
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