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Information on EC 3.5.1.114 - N-acyl-aromatic-L-amino acid amidohydrolase and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC3.5.1.114
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IUBMB Comments
This enzyme is found in animals and is involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate). It preferentially deacetylates Nalpha-acetylated aromatic amino acids and mercapturic acids (S-conjugates of N-acetyl-L-cysteine) that are usually not deacetylated by EC 3.5.1.14, N-acyl-aliphatic-L-amino acid amidohydrolase. The enzyme is significantly activated by Co2+ and Ni2+ . Some bacterial aminoacylases demonstrate substrate specificity for both EC 3.5.1.14 and EC 3.5.1.114. cf. EC 3.5.1.14, N-acyl-aliphatic-L-amino acid amidohydrolase and EC 3.5.1.15, aspartoacylase.
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Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
aminoacylase iii, n-acyl-aromatic-l-amino acid amidohydrolase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
aminoacylase 3
-
SYSTEMATIC NAME
IUBMB Comments
N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming)
This enzyme is found in animals and is involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate). It preferentially deacetylates Nalpha-acetylated aromatic amino acids and mercapturic acids (S-conjugates of N-acetyl-L-cysteine) that are usually not deacetylated by EC 3.5.1.14, N-acyl-aliphatic-L-amino acid amidohydrolase. The enzyme is significantly activated by Co2+ and Ni2+ [3]. Some bacterial aminoacylases demonstrate substrate specificity for both EC 3.5.1.14 and EC 3.5.1.114. cf. EC 3.5.1.14, N-acyl-aliphatic-L-amino acid amidohydrolase and EC 3.5.1.15, aspartoacylase.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-hydroxy-2-nonenal mercapturate + H2O
?
show the reaction diagram
substrate of aminoacylase 3, not aminoacylase 1, deacetylation
-
-
?
acrolein mercapturate + H2O
?
show the reaction diagram
substrate of aminoacylase 3, not aminoacylase 1, deacetylation
-
-
?
N-acetyl-S-geranylgeranyl-L-cysteine + H2O
3-geranylgeranyl-L-cysteine + acetate
show the reaction diagram
N-acetyl-S-[(2E,6E)-farnesyl]-L-cysteine + H2O
S-[(2E,6E)-farnesyl]-L-cysteine + acetate
show the reaction diagram
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
N-acetyl-S-geranylgeranyl-L-cysteine + H2O
3-geranylgeranyl-L-cysteine + acetate
show the reaction diagram
the 90000-100000 Da AA3 form (that is detected in most hepatocellular carcinoma cell lines but not in normal hepatocytes) is functionally active and together with the normal 35000 Da AA3 form mediates the deacetylation of N-acetylfarnesylcysteine and N-acetylgeranylgeranylcysteine
-
-
?
N-acetyl-S-[(2E,6E)-farnesyl]-L-cysteine + H2O
S-[(2E,6E)-farnesyl]-L-cysteine + acetate
show the reaction diagram
the 90000-100000 Da AA3 form (that is detected in most hepatocellular carcinoma cell lines but not in normal hepatocytes) is functionally active and together with the normal 35000 Da AA3 form mediates the deacetylation of N-acetylfarnesylcysteine and N-acetylgeranylgeranylcysteine
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
metalloenzyme, highly activating
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-(4-ethoxyphenyl)-2-methylsuccinic acid
-
2-phenyl-4H-1,3-benzothiazin-4-one
-
2-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1-methyl-1Hbenzimidazole-5-sulfonamide
-
additional information
the enzyme is a metalloenzyme that is inactivated by metal chelating compounds. Molecular docking, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.14
N-acetyl-S-geranylgeranyl-L-cysteine
pH 7.5, 37°C
0.025
N-acetyl-S-[(2E,6E)-farnesyl]-L-cysteine
pH 7.5, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
7.2
N-acetyl-S-geranylgeranyl-L-cysteine
pH 7.5, 37°C
2
N-acetyl-S-[(2E,6E)-farnesyl]-L-cysteine
pH 7.5, 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
AA3 expression in the hepatocellular carcinoma cell lines is 5 to 20 times greater than in normal primary hepatocytes
Manually annotated by BRENDA team
AA3 expression in the hepatocellular carcinoma cell lines is 5 to 20 times greater than in normal primary hepatocytes
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
P20D1_HUMAN
502
1
55741
Swiss-Prot
Secretory Pathway (Reliability: 2)
ACY3_HUMAN
319
0
35241
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
SDS-PAGE, the 90000-100000 Da band is detected in most hepatocellular carcinoma cell lines but not in normal hepatocytes
35000
SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
1 * 35000, SDS-PAGE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli to homogeneity
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
N-terminally 6His-tagged enzyme is expressed in Escherichia coli
recombinant expression of the enzyme in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression is significantly elevated in the livers of hepatocellular carcinoma patients and hepatocellular carcinoma cell lines
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
expression is significantly elevated in the livers of hepatocellular carcinoma patients and hepatocellular carcinoma cell lines. Treatment of HepG2 cells with AA3 inhibitors, and HepG2 and HuH7 with AA3 siRNA significantly decreases Ras membrane association and is toxic to these HCC cell lines. AA3 inhibition may be an effective approach in the therapy of hepatocellular carcinoma and elevated AA3 expression in hepatocellular carcinoma is potentially an important diagnostic marker
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
Toxicol. Appl. Pharmacol.
263
303-314
2012
Homo sapiens (Q96HD9), Mus musculus (Q91XE4), Rattus norvegicus (Q5M876), Rattus norvegicus Wistar (Q5M876)
Manually annotated by BRENDA team
Tsirulnikov, K.; Duarte, S.; Ray, A.; Datta, N.; Zarrinpar, A.; Hwang, L.; Faull, K.; Pushkin, A.; Kurtz, I.
Aminoacylase 3 is a new potential marker and therapeutic target in hepatocellular carcinoma
J. Cancer
9
1-12
2018
Homo sapiens (Q96HD9), Homo sapiens
Manually annotated by BRENDA team