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Information on EC 4.1.1.45 - aminocarboxymuconate-semialdehyde decarboxylase and Organism(s) Homo sapiens and UniProt Accession Q8TDX5

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     4 Lyases
         4.1 Carbon-carbon lyases
             4.1.1 Carboxy-lyases
                4.1.1.45 aminocarboxymuconate-semialdehyde decarboxylase
IUBMB Comments
Product rearranges non-enzymically to picolinate.
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This record set is specific for:
Homo sapiens
UNIPROT: Q8TDX5
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
acmsd, aminocarboxymuconate-semialdehyde decarboxylase, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase, picolinic carboxylase, acmsdase, hacmsd, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase, acmsd i, acms decarboxylase, alpha-amino-beta-carboxymuconic-epsilon-semialdehyde decarboxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
-
2-amino 3-carboxymuconate 6-semialdehyde decarboxylase
-
-
3-(3-oxoprop-2-enyl)-2-aminobut-2-endioate carboxy-lyase
-
-
-
-
ACMS decarboxylase
-
-
ACMSD
ACMSD I
-
enzymatically active form
ACMSDase
-
-
alpha-Amino-beta-carboxymuconate-epsilon-semialdehade decarboxylase
-
-
-
-
alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde beta-decarboxylase
-
-
-
-
alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
-
-
Amino-carboxymuconate-semialdehyde decarboxylase
-
-
-
-
Decarboxylase, aminocarboxymuconate semialdehyde
-
-
-
-
Picolinic acid carboxylase
-
-
-
-
Picolinic acid decarboxylase
-
-
-
-
Picolinic decarboxylase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -
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
-
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-6-semialdehyde + CO2
show the reaction diagram
2-aminomuconate semialdehyde + CO2
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
show the reaction diagram
-
-
-
?
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-2-enyl)-but-2-enedioate
2-aminomuconate-6-semialdehyde + CO2
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
plays a key role in tryptophan catabolism, the enzyme regulates NAD biosynthesis from the amino acid, directly affecting quinolinate and picolinate formation
-
-
?
NATURAL SUBSTRATE
NATURAL 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-6-semialdehyde + CO2
show the reaction diagram
2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
2-aminomuconate semialdehyde + CO2
show the reaction diagram
-
key enzyme in the regulation of the tryptophan-nicotinamide adenine dinucleotide pathway
-
?
additional information
?
-
-
plays a key role in tryptophan catabolism, the enzyme regulates NAD biosynthesis from the amino acid, directly affecting quinolinate and picolinate formation
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
1.0 mM, increases activity to 130%
Fe2+
-
0.1 mM, increases activity to 124%
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,3-dihydroxyacetonephosphate
-
3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid
potent and selective inhibitor. Treatment of primary hepatocytes significantly increases intracellular NAD+ levels. compound exhibits good solubility with low permeability of cells and no inhibition of cytochrome P450s
p-chloromercuribenzoate
-
Cd2+
-
0.5 mM, reduces the enzymatic activity to 25%
Cr3+
-
0.5 mM, reduces the enzymatic activity to 35%
Fe3+
-
0.1 mM, reduces the enzymatic activity to 15%
Kynurenic acid
-
1 mM, 59% residual activity
mono (2-ethylhexyl) phthalate
-
92% inhibition of ACMSD activity in the presence of 3 mmol/l mono (2-ethyl hexyl) phthalate, inhibition is reversible
mono-n-butyl phthalate
-
18% inhibition of ACMSD activity in the presence of 3 mmol/l mono-n-butyl phthalate
mono-n-hexyl phthalate
-
84% inhibition of ACMSD activity in the presence of 3 mmol/l mono-n-hexyl phthalate
Picolinic acid
-
1 mM, 47% residual activity
quinolinic acid
-
1 mM, 61% residual activity
Zn2+
-
0.1 mM, reduces the enzymatic activity to 6%
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0033
2-aminomuconate semialdehyde
Cu-substituted enzyme, pH 7.0, temperature not specified in the publication
0.0065
2-amino-3-(3-oxoprop-2-enyl)-but-2-enedioate
-
in 50 mM 4-morpholinepropanesulfonic acid, pH 6.0, at 25°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1 - 4.8
2-aminomuconate semialdehyde
1
2-amino-3-(3-oxoprop-2-enyl)-but-2-enedioate
-
in 50 mM 4-morpholinepropanesulfonic acid, pH 6.0, at 25°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000013
3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid
Homo sapiens
37°C, pH not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.8
recombinant enzyme, pH 7.0, temperature not specified in the publication
3.54
recombinant enzyme, presence of Zn2+ in expression medium, pH 7.0, temperature not specified in the publication
0.006
-
crude cell extract, in 50 mM 4-morpholinepropanesulfonic acid, pH 6.0, at 25°C
0.36
-
enzyme assay performed at 25°C, pH 8.0 and 50 mmol/l Tris-acetate buffer
1.39
-
after 231fold purification, in 50 mM 4-morpholinepropanesulfonic acid, pH 6.0, at 25°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ACMSD_HUMAN
336
1
38035
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40000
-
SDS-PAGE
50000
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
-
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
EPR spectroscopic study on the Cu-substituted enzyme and crystal structure in the native catalytically active state at 1.99 A resolution, a substrate analogue-bound form at 2.50 A resolution, and a selected active site mutant form with one of the putative substrate binding residues altered at 2.32 A resolution. Each asymmetric unit contains three pairs of dimers. The substrate analogue does not directly coordinate to the metal ion but is bound to the active site by two arginine residues through noncovalent interactions
molecular docking of inhibitor 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid. The 2-thiophene ring fits the hydrophobic cleft defined by the Trp191 and Met180 residues
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 20°C
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H6A
-
activity decreases by about 82%
H8A
-
activity decreases by about 50%
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
-20
-
the purified protein is sensitive to freezing at -20°C
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-78°C, enzyme endures freeze/thaw cycles multiple times without a significant loss of activity
4°C, stable for weeks
4°C, 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
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cDNA cloning, expressed in COS7 cells
expression in Escherichia coli
expression in Pichia pastoris
cDNA cloning
-
expressed in Pichia pastoris GS115 cells
-
expression in COS-7 cells
-
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
medicine
-
the enzyme is an therapeutic target for treating disorders associated with increased levels of tryptophan metabolites
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fukuoka, S.; Tanabe, A.; Egashira, Y.; Sanada, H.; Shin, M.; Shibata, K.
Identification of cDNAs encoding alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSDase)
Adv. Exp. Med. Biol.
467
615-618
1999
Caenorhabditis elegans, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Fukuoka, S.; Ishiguro, K.; Yanagihara, K.; Tanabe, A.; Egashira, Y.; Sanada, H.; Shibata, K.
Identification and expression of a cDNA encoding human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD). A key enzyme for the tryptophan-niacine pathway and "quinolinate hypothesis"
J. Biol. Chem.
277
35162-35167
2002
Homo sapiens (Q8TDX5), Homo sapiens, Mus musculus (Q8R519), Mus musculus ICR (Q8R519), Rattus norvegicus (Q8R5M5), Sus scrofa
Manually annotated by BRENDA team
Fukuwatari, T.; Ohsaki, S.; Fukuoka, S.; Sasaki, R.; Shibata, K.
Phthalate esters enhance quinolinate production by inhibiting alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), a key enzyme of the tryptophan pathway
Toxicol. Sci.
81
302-308
2004
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Pucci, L.; Perozzi, S.; Cimadamore, F.; Orsomando, G.; Raffaelli, N.
Tissue expression and biochemical characterization of human 2-amino 3-carboxymuconate 6-semialdehyde decarboxylase, a key enzyme in tryptophan catabolism
FEBS J.
274
827-840
2007
Homo sapiens
Manually annotated by BRENDA team
Garavaglia, S.; Perozzi, S.; Galeazzi, L.; Raffaelli, N.; Rizzi, M.
The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis
FEBS J.
276
6615-6623
2009
Homo sapiens (Q8TDX5), Homo sapiens
Manually annotated by BRENDA team
Pellicciari, R.; Liscio, P.; Giacche, N.; De Franco, F.; Carotti, A.; Robertson, J.; Cialabrini, L.; Katsyuba, E.; Raffaelli, N.; Auwerx, J.
alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) inhibitors as novel modulators of de novo nicotinamide adenine dinucleotide (NAD+) biosynthesis
J. Med. Chem.
61
745-759
2018
Homo sapiens (Q8TDX5)
Manually annotated by BRENDA team
Huo, L.; Liu, F.; Iwaki, H.; Li, T.; Hasegawa, Y.; Liu, A.
Human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) a structural and mechanistic unveiling
Proteins
83
178-187
2015
Homo sapiens (Q8TDX5)
Manually annotated by BRENDA team
Brundin, L.; Sellgren, C.; Lim, C.; Grit, J.; Palsson, E.; Landen, M.; Samuelsson, M.; Lundgren, K.; Brundin, P.; Fuchs, D.; Postolache, T.; Traskman-Bendz, L.; Guillemin, G.; Erhardt, S.
An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
Transl. Psychiatry
6
e865
2016
Homo sapiens (Q8TDX5), Homo sapiens
Manually annotated by BRENDA team