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Literature summary for 3.5.1.114 extracted from

  • Tsirulnikov, K.; Abuladze, N.; Bragin, A.; Faull, K.; Cascio, D.; Damoiseaux, R.; Schibler, M.J.; Pushkin, A.
    Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal (2012), Toxicol. Appl. Pharmacol., 263, 303-314.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of the enzyme in Escherichia coli Mus musculus
recombinant expression of the enzyme in Escherichia coli Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2-((E)-[(4H-1,2,4-triazol-4-yl)imino]methyl)-1-benzothiophene-3-ol
-
Rattus norvegicus
2-(4-ethoxyphenyl)-2-methylsuccinic acid
-
Homo sapiens
2-(4-ethoxyphenyl)-2-methylsuccinic acid
-
Mus musculus
2-(4-ethoxyphenyl)-2-methylsuccinic acid
-
Rattus norvegicus
2-([(3-fluoro-4-methoxyphenyl)methyl]sulfanyl)-1-methyl-1H-benzimidazole-5-sulfonamide
-
Rattus norvegicus
2-([2-chloro-4-(thiocyanato)phenyl]carbamoyl)benzoic acid
-
Rattus norvegicus
2-[(1,3-benzothiazol-2-yl)sulfanyl]ethan-1-amine
-
Rattus norvegicus
clioquinol
-
Rattus norvegicus
ebselen
-
Homo sapiens
ebselen
-
Mus musculus
ebselen
-
Rattus norvegicus
Ibuprofen
-
Mus musculus
additional information the enzyme is a metalloenzyme that is inactivated by metal chelating compounds. Molecular docking, overview Homo sapiens
additional information the enzyme is a metalloenzyme that is inactivated by metal chelating compounds. Molecular docking, overview Mus musculus
additional information the enzyme is a metalloenzyme that is inactivated by metal chelating compounds. Molecular docking, overview Rattus norvegicus
N-(2,3,5-trichloro-4-oxocyclohexa-2,5-dien-1-ylidene)benzenesulfonamide
-
Rattus norvegicus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Michaelis-Menten kinetics Mus musculus
0.2
-
4-hydroxy-2-nonenal mercapturate pH and temperature not specified in the publication, absence of Co2+ Mus musculus
0.3
-
N-acetyl-L-tyrosine pH and temperature not specified in the publication, presence of Co2+ Mus musculus
0.45
-
N-acetyl-L-tyrosine pH and temperature not specified in the publication, absence of Co2+ Mus musculus
0.53
-
4-hydroxy-2-nonenal mercapturate pH and temperature not specified in the publication, presence of Co2+ Mus musculus
0.56
-
N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine pH and temperature not specified in the publication, presence of Co2+ Mus musculus
0.71
-
acrolein mercapturate pH and temperature not specified in the publication, presence of Co2+ Mus musculus
0.82
-
acrolein mercapturate pH and temperature not specified in the publication, absence of Co2+ Mus musculus
1.3
-
N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine pH and temperature not specified in the publication, absence of Co2+ Mus musculus

Metals/Ions

Metals/Ions Comment Organism Structure
Co2+ metalloenzyme, highly activating Mus musculus
Co2+ metalloenzyme, highly activating Rattus norvegicus
Co2+ metalloenzyme, highly activating Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q96HD9
-
-
Mus musculus Q91XE4
-
-
Rattus norvegicus Q5M876
-
-
Rattus norvegicus Wistar Q5M876
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme from Escherichia coli to homogeneity Mus musculus
recombinant enzyme from Escherichia coli to homogeneity Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
blood vessel
-
Mus musculus
-
blood vessel
-
Rattus norvegicus
-
blood vessel
-
Homo sapiens
-
brain cortex
-
Mus musculus
-
brain cortex
-
Rattus norvegicus
-
brain cortex
-
Homo sapiens
-
hippocampus
-
Rattus norvegicus
-
neuron
-
Rattus norvegicus
-
neuron
-
Homo sapiens
-
neuron mainly Mus musculus
-
neuronal cell
-
Mus musculus
-
neuronal cell
-
Homo sapiens
-
neuronal cell hippocampal Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4-hydroxy-2-nonenal mercapturate + H2O substrate of aminoacylase 3, not aminoacylase 1, deacetylation Mus musculus ?
-
?
4-hydroxy-2-nonenal mercapturate + H2O substrate of aminoacylase 3, not aminoacylase 1, deacetylation Rattus norvegicus ?
-
?
4-hydroxy-2-nonenal mercapturate + H2O substrate of aminoacylase 3, not aminoacylase 1, deacetylation Homo sapiens ?
-
?
4-hydroxy-2-nonenal mercapturate + H2O substrate of aminoacylase 3, not aminoacylase 1, deacetylation Rattus norvegicus Wistar ?
-
?
acrolein mercapturate + H2O substrate of aminoacylase 3, not aminoacylase 1, deacetylation Mus musculus ?
-
?
acrolein mercapturate + H2O substrate of aminoacylase 3, not aminoacylase 1, deacetylation Rattus norvegicus ?
-
?
acrolein mercapturate + H2O substrate of aminoacylase 3, not aminoacylase 1, deacetylation Homo sapiens ?
-
?
acrolein mercapturate + H2O substrate of aminoacylase 3, not aminoacylase 1, deacetylation Rattus norvegicus Wistar ?
-
?
N-acetyl-L-tyrosine + H2O
-
Mus musculus acetate + L-tyrosine
-
?
N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine + H2O
-
Mus musculus acetate + S-(1,2-dichlorovinyl)-L-cysteine
-
?

Synonyms

Synonyms Comment Organism
AA3
-
Mus musculus
AA3
-
Rattus norvegicus
AA3
-
Homo sapiens
aminoacylase 3
-
Mus musculus
aminoacylase 3
-
Rattus norvegicus
aminoacylase 3
-
Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.13
-
N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine pH and temperature not specified in the publication, absence of Co2+ Mus musculus
0.27
-
4-hydroxy-2-nonenal mercapturate pH and temperature not specified in the publication, absence of Co2+ Mus musculus
0.28
-
N-acetyl-L-tyrosine pH and temperature not specified in the publication, absence of Co2+ Mus musculus
0.4
-
acrolein mercapturate pH and temperature not specified in the publication, absence of Co2+ Mus musculus
1.09
-
N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine pH and temperature not specified in the publication, presence of Co2+ Mus musculus
1.67
-
4-hydroxy-2-nonenal mercapturate pH and temperature not specified in the publication, presence of Co2+ Mus musculus
2.28
-
N-acetyl-L-tyrosine pH and temperature not specified in the publication, presence of Co2+ Mus musculus
3.03
-
acrolein mercapturate pH and temperature not specified in the publication, presence of Co2+ Mus musculus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00000063
-
pH and temperature not specified in the publication Rattus norvegicus 2-(4-ethoxyphenyl)-2-methylsuccinic acid
0.0000032
-
pH and temperature not specified in the publication Rattus norvegicus N-(2,3,5-trichloro-4-oxocyclohexa-2,5-dien-1-ylidene)benzenesulfonamide
0.00004
-
pH and temperature not specified in the publication Rattus norvegicus 2-([2-chloro-4-(thiocyanato)phenyl]carbamoyl)benzoic acid
0.000079
-
pH and temperature not specified in the publication Rattus norvegicus 2-([(3-fluoro-4-methoxyphenyl)methyl]sulfanyl)-1-methyl-1H-benzimidazole-5-sulfonamide
0.0016
-
pH and temperature not specified in the publication Rattus norvegicus 2-[(1,3-benzothiazol-2-yl)sulfanyl]ethan-1-amine
0.0101
-
pH and temperature not specified in the publication Rattus norvegicus clioquinol
0.063
-
pH and temperature not specified in the publication Rattus norvegicus 2-((E)-[(4H-1,2,4-triazol-4-yl)imino]methyl)-1-benzothiophene-3-ol
10
-
pH and temperature not specified in the publication Rattus norvegicus ebselen

General Information

General Information Comment Organism
malfunction aminoacylase 3 inhibition completely protects rat brain cortex neurons expressing the enzyme from the toxicity of 4-hydroxy-2-nonenal-mercapturate. 4-hydroxy-2-nonenal-cysteine is also neurotoxic and its toxicity is mostly prevented by a beta-lyase inhibitor, aminooxyacetate Mus musculus
malfunction aminoacylase 3 inhibition completely protects rat brain cortex neurons expressing the enzyme from the toxicity of 4-hydroxy-2-nonenal-mercapturate. 4-hydroxy-2-nonenal-cysteine is also neurotoxic and its toxicity is mostly prevented by a beta-lyase inhibitor, aminooxyacetate Rattus norvegicus
malfunction aminoacylase 3 inhibition completely protects rat brain cortex neurons expressing the enzyme from the toxicity of 4-hydroxy-2-nonenal-mercapturate. 4-hydroxy-2-nonenal-cysteine is also neurotoxic and its toxicity is mostly prevented by a beta-lyase inhibitor, aminooxyacetate Homo sapiens
physiological function the enzyme cleaves the conjugates 4-hydroxy-2-nonenal mercapturate and acrolein mercapturate formed by reaction with glutathione for detoxification in the GSH-conjugation pathway, overview. Aminoacylase 3 is involved in the neurotoxicity of the compounds 4-hydroxy-2-nonenal and acrolein Mus musculus
physiological function the enzyme cleaves the conjugates 4-hydroxy-2-nonenal mercapturate and acrolein mercapturate formed by reaction with glutathione for detoxification in the GSH-conjugation pathway, overview. Aminoacylase 3 is involved in the neurotoxicity of the compounds 4-hydroxy-2-nonenal and acrolein Rattus norvegicus
physiological function the enzyme cleaves the conjugates 4-hydroxy-2-nonenal mercapturate and acrolein mercapturate formed by reaction with glutathione for detoxification in the GSH-conjugation pathway, overview. Aminoacylase 3 is involved in the neurotoxicity of the compounds 4-hydroxy-2-nonenal and acrolein Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.1
-
N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine pH and temperature not specified in the publication, absence of Co2+ Mus musculus
0.49
-
acrolein mercapturate pH and temperature not specified in the publication, absence of Co2+ Mus musculus
0.62
-
N-acetyl-L-tyrosine pH and temperature not specified in the publication, absence of Co2+ Mus musculus
1.35
-
4-hydroxy-2-nonenal mercapturate pH and temperature not specified in the publication, absence of Co2+ Mus musculus
1.93
-
N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine pH and temperature not specified in the publication, presence of Co2+ Mus musculus
3.15
-
4-hydroxy-2-nonenal mercapturate pH and temperature not specified in the publication, presence of Co2+ Mus musculus
4.27
-
acrolein mercapturate pH and temperature not specified in the publication, presence of Co2+ Mus musculus
7.6
-
N-acetyl-L-tyrosine pH and temperature not specified in the publication, presence of Co2+ Mus musculus