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Information on EC 3.5.1.15 - aspartoacylase and Organism(s) Homo sapiens
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3.5.1.15 aspartoacylaseSpecify your search results
Word Map
- 3.5.1.15
- canavan
- n-acetylaspartate
- leukodystrophy
- matter
- myelin
- oligodendrocyte
-
spongy
- n-acetyl-l-aspartate
-
spongiform
- macrocephaly
- tremor
-
ashkenazi
-
jewish
-
non-jewish
-
dysmyelination
- nutrition
- medicine
- pharmacology
- n-acetylaspartylglutamate
- triacetate
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
aspartoacylase, human aspa, haspa, aspartoacylase ii, murine aspartoacylase, aminoacylase 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetyl-aspartic deaminase
-
-
-
-
Acylase II
-
-
-
-
Aminoacylase II
-
-
-
-
ASPA
Aspartoacylase
N-Acetyl-L-aspartate amidohydrolase
-
-
-
-
N-Acetylaspartate amidohydrolase
-
-
-
-
additional information
-
the enzyme belongs to the carboxypeptidase metalloprotein family
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N-acyl-L-aspartate + H2O = a carboxylate + L-aspartate
reaction mechanism involving Glu178, molecular modeling
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of amide bond
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
N-acyl-L-aspartate amidohydrolase
-
CAS REGISTRY NUMBER
COMMENTARY
9031-86-1
-
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
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetylasparagine + H2O
acetate + aspartate + NH3
-
10% of the activity towards N-acetylaspartate
product is aspartate, not asparagine, indicating the enzyme catalyzes deacetylation as well as hydrolysis of the beta acid amide
?
N-acetylaspartate + H2O
L-aspartate + acetate
-
aspartocylase deficiency results in elevated levels of substrate, brain edema and dysmyelination
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-trifluoroacetyl-L-aspartate + H2O
trifluoroacetate + L-aspartate
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
aspartoacylase is a key enzyme in the human central nervous system. N-Acetyl-L-aspartate is a precursor for the synthesis of the dipeptide N-acetylaspartyl-glutamate, which participates in the neuromodulation of metabotropic and NMDA receptors (NMDA is N-methyl-D-aspartate), regulates the intracellular pressure in neurons and is involved in the energy generation from glutamate anions in neuronal mitochondria. N-Acetyl-L-aspartate is a source of acetyl groups for the construction of myelin sheath in the brain. Therefore, maintenance of the N-acetyl-L-aspartate level ensures proper development and functions of white matter
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
the enzyme hydrolyzes one of the most abundant amino acid derivatives in the brain, N-acetyl-aspartate
-
-
?
N-acetyl-L-aspartate + H2O
aspartate + acetate
enzyme mutations cause the Canavan disease
-
-
?
N-acetyl-L-aspartate + H2O
aspartate + acetate
deficiency in enzyme activity leads to spongiform degeneration of the white matter of the brain and is the established cause of Canavan disease
-
-
?
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
malfunction of the enzyme causes Canavan disease
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
enzyme deficiency causes the Canavan disease, an autosomal-recessive neurodegenerative disorder
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
enzyme mutations cause the Canavan disease
-
-
?
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
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetylaspartate + H2O
L-aspartate + acetate
-
aspartocylase deficiency results in elevated levels of substrate, brain edema and dysmyelination
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
aspartoacylase is a key enzyme in the human central nervous system. N-Acetyl-L-aspartate is a precursor for the synthesis of the dipeptide N-acetylaspartyl-glutamate, which participates in the neuromodulation of metabotropic and NMDA receptors (NMDA is N-methyl-D-aspartate), regulates the intracellular pressure in neurons and is involved in the energy generation from glutamate anions in neuronal mitochondria. N-Acetyl-L-aspartate is a source of acetyl groups for the construction of myelin sheath in the brain. Therefore, maintenance of the N-acetyl-L-aspartate level ensures proper development and functions of white matter
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
the enzyme hydrolyzes one of the most abundant amino acid derivatives in the brain, N-acetyl-aspartate
-
-
?
N-acetyl-L-aspartate + H2O
aspartate + acetate
enzyme mutations cause the Canavan disease
-
-
?
N-acetyl-L-aspartate + H2O
aspartate + acetate
deficiency in enzyme activity leads to spongiform degeneration of the white matter of the brain and is the established cause of Canavan disease
-
-
?
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
malfunction of the enzyme causes Canavan disease
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
enzyme deficiency causes the Canavan disease, an autosomal-recessive neurodegenerative disorder
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
enzyme mutations cause the Canavan disease
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
Zn2+
-
metallopeptidase, the enzyme contains the conserved H21XXE24(91aa)H116 motif, ligand binding by His21, Glu24, and His116, molecular modeling
Zn2+
-
required for activity, spectroscopical determination of metal content, the enzyme contains about 1 Zn2+ per enzyme subunit
Zn2+
necessary for activity, coordinated by residues His-21, Glu-24, and His-116 and a phosphate
Zn2+
zinc-dependent enzyme. Zn2+ coordination region: His21, Glu24 and His116
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-acetyl-aspartate
decrease of the reaction rate at high substrate concentrations. Binding of N-acetyl-aspartate to the allosteric site induces significant rigidity to the protein loops with the amino acid side chains forming gates to the enzyme active site
N-acetyl-L-aspartate
at low N-acetyl-L-aspartate concentrations, sigmoidal shape of kinetic curve is observed, followed by typicalrate growth of the enzyme-catalyzed reaction, whereas at high concentrations of N-acetyl-L-aspartate self-inhibition takes place. N-Acetylaspartate acts as activator at low concentrations, substrate at moderate concentrations, and inhibitor at high concentrations
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-acetylaspartate
N-acetylaspartate acts as activator at low concentrations, substrate at moderate concentrations, and inhibitor at high concentrations
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.36
N-acetyl-L-aspartate
pH and temperature not specified in the publication
0.59
N-Chloroacetyl-L-aspartate
pH and temperature not specified in the publication
0.23
N-dichloroacetyl-L-aspartate
pH and temperature not specified in the publication
0.95
N-formyl-L-aspartate
pH and temperature not specified in the publication
0.21
N-trifluoroacetyl-L-aspartate
pH and temperature not specified in the publication
additional information
additional information
-
the enzyme shows sigmoidal behaviour and cooperative substrate bindng at low substrate concentration of 0.05-0.2 mM
-
0.12
N-acetylaspartic acid
-
pH 7.2, recombinant Pichia pastoris-expressed enzyme
0.36
N-acetylaspartic acid
-
pH 7.2, recombinant Escherichia coli-expressed enzyme
0.15
N-trifluoroacetylaspartic acid
-
pH 7.2, recombinant Pichia pastoris-expressed enzyme
0.21
N-trifluoroacetylaspartic acid
-
pH 7.2, recombinant Escherichia coli-expressed enzyme
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.083
N-acetyl-L-aspartate
pH and temperature not specified in the publication
0.62
N-Chloroacetyl-L-aspartate
pH and temperature not specified in the publication
0.77
N-dichloroacetyl-L-aspartate
pH and temperature not specified in the publication
0.25
N-formyl-L-aspartate
pH and temperature not specified in the publication
1.2
N-trifluoroacetyl-L-aspartate
pH and temperature not specified in the publication
0.083
N-acetylaspartic acid
-
pH 7.2, recombinant Escherichia coli-expressed enzyme
12.7
N-acetylaspartic acid
-
pH 7.2, recombinant Pichia pastoris-expressed enzyme
1.2
N-trifluoroacetylaspartic acid
-
pH 7.2, recombinant Escherichia coli-expressed enzyme
116
N-trifluoroacetylaspartic acid
-
pH 7.2, recombinant Pichia pastoris-expressed enzyme
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.23
N-acetyl-L-aspartate
pH and temperature not specified in the publication
1
N-Chloroacetyl-L-aspartate
pH and temperature not specified in the publication
3.4
N-dichloroacetyl-L-aspartate
pH and temperature not specified in the publication
0.26
N-formyl-L-aspartate
pH and temperature not specified in the publication
5.8
N-trifluoroacetyl-L-aspartate
pH and temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
57
recombinant enzyme expressed from Escherichia coli, pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
additional information
malfunction
defects in the ASPA gene that codes for aspartoacylase causes a dramatic elevation in N-acetyl-L-aspartate1 levels, depletion of brain acetate, and leads to demyelination in neuronal cellsenzyme deficiency lead to a loss of activity and the symptoms of a fatal neurological disorder called Canavan disease
malfunction
mutations in the ASPA gene cause the Canavan disease, a fatal, childhood neurological disorder leading to catalytic deficiencies in the aspartoacylase (ASPA) enzyme and impaired N-acetyl-l-aspartic acid metabolism in the brain. The mutant enzymes each have overall structures similar to that of the wild-type ASPA enzyme, but with varying degrees of alterations that offer explanations for the respective loss of catalytic activity
malfunction
mutations in the ASPA gene cause the Canavan disease, a fatal, childhood neurological disorder leading to catalytic deficiencies in the aspartoacylase enzyme and impaired N-acetyl-L-aspartic acid metabolism in the brain. Enzyme replacement therapy can potentially be used to overcome these defects if a stable enzyme form that can gain access to the appropriate neural cells can be produced. Achieving the proper cellular targeting requires a modified form of aspartoacylase that can traverse the blood-brain barrier
malfunction
catalytic deficiency of aspartoacylase is associated with several neurodegenerative disorders. The Canavan disease occurs most frequently in Ashkenazi Jews, with more than 96% of cases being associated with two point mutations: Glu285Ala and Tyr231X. The Canavan disease in other ethnic groups is associated with a more diverse range of mutations, the Ala305Glu replacement being the most frequent
malfunction
mutations in the ASPA gene are associated with the development of Canavan disease (CD), leading to the deficiency of ASPA activity. Patients with CD are characterized by degeneration of the white matter of the brain
physiological function
aspartoacylase catalyzes the selective breakdown of N-acetyl-L-aspartate to release acetate in the brain. The acetate provides the building blocks required for fatty acid biosynthesis
physiological function
aspartoacylase is a key enzyme in the human central nervous system
additional information
homology modeling of the N117Q human aspartoacylase mutant using the native structure, PDB ID 2O53, as the template
additional information
-
homology modeling of the N117Q human aspartoacylase mutant using the native structure, PDB ID 2O53, as the template
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ACY2_HUMAN
313
0
35735
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
36000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
additional information
additional information
-
the enzyme belongs to the carboxypeptidase metalloprotein family with the conserved H21XXE24(91aa)H116 motif
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
carbohydrate determination by mass spectrometry, overview, the N-glycosylation site is N117
glycoprotein
presence of a glycan at Asn117 that plays an essential role in the stability and catalytic activity of mammalian aspartoacylase. Although recombinantly-expressed human aspartoacylase is not glycosylated, mass spectrometric analysis, overview. The recombinant enzyme is still fully functional and stable, even when produced from a bacterial expression system
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystallization in complex with inhibitor N-phosphonomethyl-L-aspartate, crystallization conditions: 50 mM sodium citrate (pH 6.0), 300 mM K2HPO4, and 15-19% polyethylene glycol 3350
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A305E
C152R
0.5% activity compared to native enzyme form, the stabilities against denaturation induced by heating and by a 1 M urea solution (conformational stability) are considerably lower for the mutant than for native form of the enzyme, mutation responsible for the Canavan disease
C152W
E178D
E24A
E24D
E24G
E285A
E285A/P181T
32% activity compared to native enzyme form, the stabilities against denaturation induced by heating and by a 1 M urea solution (conformational stability) are considerably lower for the mutant than for native form of the enzyme, mutation responsible for the Canavan disease
F295S
H116A
H21A
I143V
the pathogenicity, stability, conservation, change in structural pattern, influence of the mutations on substrate binding of the crystallized mutations (K213E, Y231C, E285A, F295S, I143V and V186D) is compared. The binding affinity to the substrate, hydrogen bond interactions and metal interactions are found to be highly disturbed due to the mutant V186D than the mutant I143V
I143V/V186D
patients with severe form of Canavan disease (CD) have both missense mutations in the ASPA: c.427 A > G; p. I143V and c.557 T > A; p. V186D. Patient 1 harbors both mutations (p.I143V and p.V186D) in a heterozygous form together with four other mutations, and patient 2 has both mutations in homozygous form
I226T
-
mutant shows no catalytic activity, mutation may be responsible in homozygosis for the phenotype corresponding to Canavan disease.
K213E
N117Q
R63N
R71H
11% activity compared to native enzyme form, the stabilities against denaturation induced by heating and by a 1 M urea solution (conformational stability) are considerably lower for the mutant than for native form of the enzyme, mutation responsible for the Canavan disease
V186D
the pathogenicity, stability, conservation, change in structural pattern, influence of the mutations on substrate binding of the crystallized mutations (K213E, Y231C, E285A, F295S, I143V and V186D) is compared. The binding affinity to the substrate, hydrogen bond interactions and metal interactions are found to be highly disturbed due to the mutant V186D than the mutant I143V. The mutant V186D can be more pathogenic than the mutant I143V
Y231C
additional information
A305E
10% activity compared to native enzyme form, mutation responsible for the Canavan disease
C152W
1% activity compared to native enzyme form, the stabilities against denaturation induced by heating and by a 1 M urea solution (conformational stability) are considerably lower for the mutant than for native form of the enzyme, mutation responsible for the Canavan disease
E178D
-
site-directed mutagenesis, the mutant shows reduced catalytic activity compared to the wild-type enzyme
E285A
a naturally occuring missense mutation associated with the Canavan disease, the mutant shows loss of hydrogen bonding interactions with the carboxylate side chain of Glu285, which disturbs the active site architecture leading to altered substrate binding and lower catalytic activity
E285A
0.3% activity compared to native enzyme form, the stabilities against denaturation induced by heating and by a 1 M urea solution (conformational stability) are considerably lower for the mutant than for native form of the enzyme, mutation responsible for the Canavan disease
E285A
the pathogenicity, stability, conservation, change in structural pattern, influence of the mutations on substrate binding of the crystallized mutations (K213E, Y231C, E285A, F295S, I143V and V186D) is compared. Of the crystallized mutations, the mutant E285A is found to be highly conserved as well as affecting the substrate binding with lesser number of overall hydrogen bonds
F295S
a naturally occuring missense mutation associated with the Canavan disease, the mutant shows loss of van der Waals contacts
F295S
10% activity compared to native enzyme form, the stabilities against denaturation induced by heating and by a 1 M urea solution (conformational stability) are considerably lower for the mutant than for native form of the enzyme, mutation responsible for the Canavan disease
F295S
the decreased availability of the active site for substrate molecules in the mutated enzymes explains their diminishing activity observed in clinical experiments. The variant is associated with the mild or variable form of Canavan disease
F295S
the pathogenicity, stability, conservation, change in structural pattern, influence of the mutations on substrate binding of the crystallized mutations (K213E, Y231C, E285A, F295S, I143V and V186D) is compared
K213E
a naturally occuring missense mutation associated with a mild phenotype of Canavan disease, a nonconservative mutant, has minimal structural differences compared to the wild-type enzyme
K213E
the pathogenicity, stability, conservation, change in structural pattern, influence of the mutations on substrate binding of the crystallized mutations (K213E, Y231C, E285A, F295S, I143V and V186D) is compared. The mutant K213E is found to be least conserved, and the substrate binding affinity is found to be minimal
K213E
the point mutation does not affect the catalytic function of the enzyme
N117Q
-
site-directed mutagenesis, the mutant enzyme is less stable than the wild-type enzyme, while it shows similar catalytic properties and substrate specificity
N117Q
homology modeling of the N117Q human aspartoacylase mutant using the native structure, PDB ID 2O53, as the template
Y231C
a naturally occuring missense mutation associated with the Canavan disease, the mutant shows loss of hydrophobic and hydrogen bonding interactions. The mutation leads to a local collapse of the hydrophobic core structure in the carboxyl-terminal domain, contributing to a decrease in protein stability
Y231C
24% activity compared to native enzyme form, the stabilities against denaturation induced by heating and by a 1 M urea solution (conformational stability) are considerably lower for the mutant than for native form of the enzyme, mutation responsible for the Canavan disease
Y231C
the decreased availability of the active site for substrate molecules in the mutated enzymes explains their diminishing activity observed in clinical experiments. The variant is associated with the mild or variable form of Canavan disease
Y231C
the pathogenicity, stability, conservation, change in structural pattern, influence of the mutations on substrate binding of the crystallized mutations (K213E, Y231C, E285A, F295S, I143V and V186D) is compared
additional information
-
Canavan disease is a rare recessive genetic neurodegenerative brain disorder that is associated with many different mutations in the gene encoding aspartoacylase
additional information
synthesis of PEGylated enzyme by treatment of enzyme samples with amethoxy-PEG reagent containing terminal activating aldehyde or ester groups attached with a carboxymethyl linker, purification of the protein-PEG conjugates by anion exchange chromatography, labeling with a covalently attached fluorescent tag, method optimization, overview
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PEGylated forms of aspartoacylase (modified with PEG of 2 kDa, 5 kDa, 10 kDa, 20 kDa or 40 kDa) show similar activities to that of the native enzyme. The activity of PEGylated enzyme samples is monitored for 72 hours without observing a substantial loss in activity
-
the Escherichia coli-expressed enzyme form is quite unstable, losing a significant fraction of its catalytic activity within 24 h
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
the Pichia pastoris-expressed enzyme shows sensitivity to oxidation over time and will precipitate if not kept under the proper reducing conditions, addition of 1 mM DTT reverses the precipitated state of the enzyme with no significant loss of activity
-
667727
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
the purified enzyme expressed in Pichia pastoris is significantly more stable than the Escherichia coli-expressed enzyme, losing less than 10% of its catalytic activity after 2 weeks when stored under conditions where the Escherichia coli-expressed enzyme becomes completely inactivated within 24 h, the Pichia pastoris-expressed enzyme shows sensitivity to oxidation over time and will precipitate if not kept under the proper reducing conditions
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme by metal affinity chromatography, dialysis, and anion exchange chromatography
-
recombinant His-tagged enzyme from Pichia pastoris strain KM71H by nickel affinity chromatography, dialysis, and anion exchange chromatography
recombinant wild-type and mutant GST-fusion enzymes from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression of wild-type and mutant enzymes as GST-fusion proteins in Escherichia coli strain BL21(DE3)
-
gene acy2 or ASPA, recombinant expression of His-tagged enzyme in Pichia pastoris strain KM71H and in Escherichia coli. Recombinantly-expressed human aspartoacylase is not glycosylated, but is still fully functional and stable even when produced from a bacterial expression system
stable expression of wild-type and mutant enzyme in Pichia pastoris, expression in Escherichia coli strain XL10 primarily in inclusion bodies, while the expression yields are lower in Pichia pastoris than in Escherichia coli, the purified enzyme is significantly more stable, the enzyme form has the same substrate specificity but is 150fold more active than the Escherichia coli-expressed enzyme
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
the Pichia pastoris-expressed wild-type enzyme shows sensitivity to oxidation over time and will precipitate if not kept under the proper reducing conditions, addition of 1 mM DTT reverses the precipitated state of the enzyme with no significant loss of activity
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
pharmacology
the enzyme is the taget for treatment of Canavan disease, enzyme replacement therapy can potentially be used to overcome these defects if a stable enzyme form that can gain access to the appropriate neural cells can be produced. PEGylated form of aspartoacylase are able to traverse the blood-brain barrier and show dramatic enhancement in brain tissue access and distribution, overview. Examination of the effect of enzyme administration on the immunological response
medicine
-
diagnosis of Canavan disease, an autosomal recessive neurodegenerative disorder characterized by aspartoacylase deficiency, technique for prenatal diagnosis
medicine
-
mutations in the aspartoacylase aspA gene are implicated as the cause of Canavan Disease
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kaul, R.; Casanova, J.; Johnson, A.B.; Tang, P.; Matalon, R.
Purification, characterization, and localization of aspartoacylase from bovine brain
J. Neurochem.
56
129-135
1991
Bos taurus, Homo sapiens
Namboodiri, M.A.A.; Corigliano-Murphy, A.; Jiang, G.; Rollag, M.; Provencio, I.
Murine aspartoacylase: cloning, expression and comparison with the human enzyme
Mol. Brain Res.
77
285-289
2000
Bos taurus, Homo sapiens, Mus musculus (Q8R3P0), Mus musculus, Prochlorococcus marinus
Baslow, M.H.; Suckow, R.F.; Sapirstein, V.; Hungund, B.L.
Expression of aspartoacylase activity in cultured rat macroglial cells is limited to oligodendrocytes
J. Mol. Neurosci.
13
47-53
1999
Carassius auratus, Homo sapiens, Rattus norvegicus
Barash, V.; Flhor, D.; Morag, B.; Boneh, A.; Elpeleg, O.N.; Gilon, C.
A radiometric assay for aspartoacylase activity in human fibroblasts: application for the diagnosis of canavan's disease
Clin. Chim. Acta
201
175-182
1991
Homo sapiens, Rattus norvegicus
Le Coq, J.; An, H.J.; Lebrilla, C.; Viola, R.E.
Characterization of human aspartoacylase: the brain enzyme responsible for Canavan disease
Biochemistry
45
5878-5884
2006
Homo sapiens
Herga, S.; Berrin, J.G.; Perrier, J.; Puigserver, A.; Giardina, T.
Identification of the zinc binding ligands and the catalytic residue in human aspartoacylase, an enzyme involved in Canavan disease
FEBS Lett.
580
5899-5904
2006
Homo sapiens
Klugmann, M.; Leichtlein, C.B.; Symes, C.W.; Serikawa, T.; Young, D.; During, M.J.
Restoration of aspartoacylase activity in CNS neurons does not ameliorate motor deficits and demyelination in a model of Canavan disease
Mol. Ther.
11
745-753
2005
Homo sapiens, Rattus norvegicus
Le Coq, J.; Pavlovsky, A.; Malik, R.; Sanishvili, R.; Xu, C.; Viola, R.E.
Examination of the mechanism of human brain aspartoacylase through the binding of an intermediate analogue
Biochemistry
47
3484-3492
2008
Homo sapiens (P45381), Homo sapiens
Hershfield, J.R.; Pattabiraman, N.; Madhavarao, C.N.; Namboodiri, M.A.
Mutational analysis of aspartoacylase: implications for Canavan disease
Brain Res.
1148
1-14
2007
Homo sapiens (P45381)
Di Pietro, V.; Gambacurta, A.; Amorini, A.M.; Finocchiaro, A.; DUrso, S.; Ceccarelli, L.; Tavazzi, B.; Giardina, B.; Lazzarino, G.
A new T677C mutation of the aspartoacylase gene encodes for a protein with no enzymatic activity
Clin. Biochem.
41
611-615
2008
Homo sapiens
Bitto, E.; Bingman, C.A.; Wesenberg, G.E.; McCoy, J.G.; Phillips, G.N.
Structure of aspartoacylase, the brain enzyme impaired in Canavan disease
Proc. Natl. Acad. Sci. USA
104
456-461
2007
Rattus norvegicus, Homo sapiens (P45381), Homo sapiens
Baslow, M.H.; Guilfoyle, D.N.
Are Astrocytes the Missing Link Between Lack of Brain Aspartoacylase Activity and the Spongiform Leukodystrophy in Canavan Disease?
Neurochem. Res.
34
1523-1534
2009
Homo sapiens
Zhang, C.; Liu, X.; Xue, Y.
A general acid-general base reaction mechanism for human brain aspartoacylase: A QM/MM study
Comput. Theoret. Chem.
980
85-91
2012
Homo sapiens (P45381)
-
Durmaz, A.A.; Akin, H.; Onay, H.; Vahabi, A.; Ozkinay, F.
A novel aspartoacylase (ASPA) gene mutation in Canavan disease
Fetal. Pediatr. Pathol.
31
236-239
2012
Homo sapiens
Zhang, C.H.; Gao, J.Y.; Chen, Z.Q.; Xue, Y.
Molecular dynamics and density functional theory studies of substrate binding and catalysis of human brain aspartoacylase
J. Mol. Graph. Model.
28
799-806
2010
Homo sapiens (P45381), Homo sapiens
Zano, S.; Malik, R.; Szucs, S.; Matalon, R.; Viola, R.E.
Modification of aspartoacylase for potential use in enzyme replacement therapy for the treatment of Canavan disease
Mol. Genet. Metab.
102
176-180
2011
Homo sapiens
Wang, Q.; Viola, R.E.
Reexamination of aspartoacylase: is this human enzyme really a glycoprotein?
Arch. Biochem. Biophys.
548
66-73
2014
Homo sapiens (P45381), Homo sapiens
Wijayasinghe, Y.S.; Pavlovsky, A.G.; Viola, R.E.
Aspartoacylase catalytic deficiency as the cause of Canavan disease: a structural perspective
Biochemistry
53
4970-4978
2014
Homo sapiens (P45381)
Poddar, N.K.; Zano, S.; Natarajan, R.; Yamamoto, B.; Viola, R.E.
Enhanced brain distribution of modified aspartoacylase
Mol. Genet. Metab.
113
219-224
2014
Homo sapiens (P45381)
Kots, E.D.; Lushchekina, S.V.; Varfolomeev, S.D.; Nemukhin, A.V.
Role of protein dimeric interface in allosteric inhibition of N-acetyl-aspartate hydrolysis by human aspartoacylase
J. Chem. Inf. Model.
57
1999-2008
2017
Homo sapiens (P45381), Homo sapiens
Kots, E.D.; Khrenova, M.G.; Nemukhin, A.V.
Allosteric control of N-acetyl-aspartate hydrolysis by the Y231C and F295S mutants of human aspartoacylase
J. Chem. Inf. Model.
59
2299-2308
2019
Homo sapiens (P45381), Homo sapiens
Khrenova, M.G.; Kots, E.D.; Varfolomeev, S.D.; Lushchekina, S.V.; Nemukhin, A.V.
Three faces of N-acetylaspartate activator, substrate, and inhibitor of human aspartoacylase
J. Phys. Chem. B
121
9389-9397
2017
Homo sapiens (P45381), Homo sapiens
George Priya Doss, C.; Zayed, H.
Comparative computational assessment of the pathogenicity of mutations in the aspartoacylase enzyme
Metab. Brain Dis.
32
2105-2118
2017
Homo sapiens (P45381), Homo sapiens
Kots, E.; Khrenova, M.; Lushchekina, S.; Nemukhin, A.
Mechanisms of the aspartoacylase catalytic activity regulation according to the computer modeling results
Moscow Univ. Chem. Bull.
73
152-154
2018
Homo sapiens (P45381)
-
Kots, E.; Khrenova, M.; Nemukhin, A.; Varfolomeev, S.
Aspartoacylase A central nervous system enzyme. Structure, catalytic activity and regulation mechanisms
Russ. Chem. Rev.
88
1-26
2019
Homo sapiens (P45381)
-
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