Information on EC 4.1.1.45 - Aminocarboxymuconate-semialdehyde decarboxylase

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

EC NUMBER
COMMENTARY hide
4.1.1.45
-
RECOMMENDED NAME
GeneOntology No.
Aminocarboxymuconate-semialdehyde decarboxylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate = 2-aminomuconate semialdehyde + CO2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
2-amino-3-carboxymuconate semialdehyde degradation to 2-oxopentenoate
-
-
2-amino-3-carboxymuconate semialdehyde degradation to glutaryl-CoA
-
-
2-nitrobenzoate degradation I
-
-
Metabolic pathways
-
-
tryptophan metabolism
-
-
Tryptophan metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate carboxy-lyase (2-aminomuconate-semialdehyde-forming)
Product rearranges non-enzymically to picolinate.
CAS REGISTRY NUMBER
COMMENTARY hide
37289-47-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
nematode
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
mouse, ICR strain
SwissProt
Manually annotated by BRENDA team
strain KU-7
SwissProt
Manually annotated by BRENDA team
Wistar strain
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
the enzyme plays a key role in NAD+ biosynthesis from tryptophan. The enzyme is associated with cholesterol 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-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
2-aminomuconate semialdehyde + CO2
show the reaction diagram
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
2-aminomuconate-6-semialdehyde + CO2
show the reaction diagram
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
?
show the reaction diagram
2-amino-3-(3-oxoprop-2-enyl)-but-2-enedioate
2-aminomuconate-6-semialdehyde + CO2
show the reaction diagram
additional information
?
-
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
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
2-aminomuconate semialdehyde + CO2
show the reaction diagram
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
2-aminomuconate-6-semialdehyde + CO2
show the reaction diagram
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
?
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
MgCl2
-
slightly stimulates
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,3-dihydroxyacetonephosphate
-
2-hydroxymuconate 6-semialdehyde
-
-
Cd2+
-
0.5 mM, reduces the enzymatic activity to 25%
Cr3+
-
0.5 mM, reduces the enzymatic activity to 35%
CuSO4
-
-
diethyldicarbonate
-
-
EDTA
-
-
eicosapentaenoic acid
-
ACMSD mRNA levels in primary hepatocytes are decreased by the incubation with high concentrations of eicosapentaenoic acid
Fe3+
-
0.1 mM, reduces the enzymatic activity to 15%
HgCl2
-
-
iodoacetamide
-
-
Kynurenic acid
-
1 mM, 59% residual activity
linoleic acid
-
ACMSD mRNA levels in primary hepatocytes are decreased by the incubation with high concentrations of linoleic acid
mono (2-ethyl hexyl) phthalate
-
90% inhibition of ACMSD activity in the presence of 3 mmol/l mono (2-ethyl hexyl) phthalate, inhibition is reversible
mono (2-ethylhexyl) phthalate
mono-n-butyl phthalate
mono-n-hexyl phthalate
Monoiodoacetic acid
-
-
N-Acetylimidazole
-
-
NaF
-
-
NEM
-
-
p-chloromercuribenzoate
p-chloromercuribenzoic acid
-
-
peroxisome proliferator-activated receptor alpha
-
gene expression is downregulated by activation of peroxisome proliferator-activated receptor alpha
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Picolinic acid
-
1 mM, 47% residual activity
pyridine-2,6-dicarboxylic acid
-
competitive
quinolinic acid
-
1 mM, 61% residual activity
WY-14,643
-
ACMSD mRNA levels in primary hepatocytes are decreased by the incubation with high concentrations of WY-14,643
Zn2+
-
0.1 mM, reduces the enzymatic activity to 6%
[4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid
-
suppresses ACMSD activity
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
hepatocyte nuclear factor 4alpha
-
gene expression is activated by hepatocyte nuclear factor 4alpha
-
additional information
-
hepatic ACMSD activity is increased in streptozotocin-induced diabetic rats
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001 - 0.0161
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
0.0065 - 0.0672
2-amino-3-(3-oxoprop-2-enyl)-but-2-enedioate
0.013 - 0.014
2-amino-3-carboxymuconate-6-semialdehyde
0.0049 - 0.0921
alpha-amino-beta-carboxymuconate-epsilon-semialdehyde
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6.5
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
Pseudomonas fluorescens
-
wild type enzyme, at pH 7.0 and 22C
0.019 - 7.3
2-amino-3-(3-oxoprop-2-enyl)-but-2-enedioate
1.4 - 10.2
alpha-amino-beta-carboxymuconate-epsilon-semialdehyde
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0227
pyridine-2,6-dicarboxylic acid
-
wild type enzyme, at pH 7.0 and 22C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.006
-
crude cell extract, in 50 mM 4-morpholinepropanesulfonic acid, pH 6.0, at 25C
0.36
-
enzyme assay performed at 25C, pH 8.0 and 50 mmol/l Tris-acetate buffer
0.8
-
25 mM Hepes buffer at pH 7.0 and 25C, under not saturating conditions. ACSMD loaded with 1 molar equivalent Mn2+
1.39
-
after 231fold purification, in 50 mM 4-morpholinepropanesulfonic acid, pH 6.0, at 25C
1.7
-
25 mM Hepes buffer at pH 7.0 and 25C, under not saturating conditions. ACSMD loaded with 1 molar equivalent Cd2+
2.9
-
25 mM Hepes buffer at pH 7.0 and 25C, under not saturating conditions. ACSMD loaded with 1 molar equivalent Fe2+
3.789
-
-
5.9
-
25 mM Hepes buffer at pH 7.0 and 25C, under not saturating conditions. ACSMD loaded with 1 molar equivalent Co2+
6
-
in 25 mM HEPES buffer containing 5% glycerol, pH 7.0, at 22C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9.5
-
-
6.5 - 8
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9
-
pH 6: about 40% of maximal activity, pH 9.0: about 35% of maximal activity
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37140
deduced from DNA sequence
38090
deduced from cDNA
38700
recombinant protein, SDS-PAGE
40000
-
SDS-PAGE
50000
-
gel filtration
58000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
x-ray crystallography
monomer
monomer or dimer
-
the protein exists in solution as a mixture of both monomer and dimer forms
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
vapour diffusion technique in hanging drop, crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with the glycolytic intermediate 1,3-dihydroxyacetonephosphate (DHAP), refined to an R-factor of 0.19, 1 mM DHAP, 2% poly(ethylene glycol) (PEG 400), 0.1 M Na/Hepes pH 7.5, 2.0 M ammonium sulphate, mixed with the same amount of a protein solution at a concentration of 12.7 mg/ml, and equilibrated against 500 microL of the reservoir solution, at 20C
hanging drop vapour diffusion method with 0.1 M Tris (pH 8.75), 15% PEG 5000, and 0.2 M MgCl2, at 20C
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mutant enzymes Co(II)-H228Y, Zn(II)-H228Y, and Zn(II)-H228G, hanging drop vapor diffusion method, using 0.1 M Tris-HCl (pH 8.75), 0.2 M MgCl2, and 15% (w/v) PEG 5000
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9.5
-
stable
4567, 4568
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
-20
-
the purified protein is sensitive to freezing at -20C
40 - 60
activity is decreased by 25% after 5 min at 40C, but thereafter is stable for up to 30 min, activity is completely lost by incubation at 60C for 30 min
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 50 mM potassium phosphate buffer, pH 7.0, 0.14 M KCl, 5 mM 2-mercaptoethanol, 1 mM dithiothreitol, 1 mM EDTA, 20% glycerol, stable for at least 1 month
-
-20C, stable for several months
-
4C, 10 mM Tris-HCl, pH 8.0, 0.13 m NaCl, several weeks, remains stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydroxyapatite column chromatography, MonoQ column chromatography and Superose 12 gel filtration
-
Ni-NTA superflow resin chromatography and HisPrep FF column chromatography
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Q-Sepharose HP column chromatography, Phenyl Sepharose column chromatography
-
Superdex 75 gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA cloning
cDNA cloning, ACMSD ORF is inserted into a mammalian expression vector and transfected into human hepatoma HepG2 cells
cDNA cloning, expressed in COS7 cells
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Pichia pastoris GS115 cells
-
expression in COS-7 cells
-
nbaD gene overexpressed in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme mRNA expression and activity is decreased by phytol in a dose-dependent manner (80% at 0.1 mM)
-
gene expression is positively regulated by SREBP-2 in the hypercholesterolemic rat and rat primary hepatocytes
the enzyme activity in hypercholesterolemic rats is decreased in liver but not in kidney
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H6A
-
activity decreases by about 82%
H8A
-
activity decreases by about 50%
D294E
-
the mutation causes a dramatic loss of enzyme activity, substantial reduction of the metal-binding ability, and an altered metallocenter electronic structure
H228A
-
the mutation causes a dramatic loss of enzyme activity, substantial reduction of the metal-binding ability, and an altered metallocenter electronic structure
H228E
-
the mutation causes a dramatic loss of enzyme activity, substantial reduction of the metal-binding ability, and an altered metallocenter electronic structure
H228G
the mutant contains iron rather than zinc and is catalytically inactive
H228Y
the mutant contains iron rather than zinc and is catalytically inactive
H9E
-
the mutation causes a dramatic loss of enzyme activity, substantial reduction of the metal-binding ability, and an altered metallocenter electronic structure
R239A
-
catalytically inactive
R239K
-
catalytically inactive
R51A
-
catalytically inactive
R51K
-
catalytically inactive
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
inhibition of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase should be explored as a possible novel therapeutic avenue for the treatment of diabetes
medicine
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