Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
acetyl-DL-alanine + H2O
acetate + DL-alanine
acetyl-DL-aspartic acid + H2O
acetate + DL-aspartate
-
-
-
-
?
acetyl-DL-methionine + H2O
acetate + methionine
acetyl-L-glutamate + H2O
acetate + glutamate
acetyl-L-leucine + H2O
acetate + leucine
chloroacetyl-DL-alanine + H2O
chloroacetate + DL-alanine
chloroacetyl-DL-aspartic acid + H2O
chloroacetate + DL-aspartate
-
-
-
-
?
chloroacetyl-DL-glutamic acid + H2O
chloroacetate + DL-glutamate
-
-
-
-
?
chloroacetyl-DL-leucine + H2O
chloroacetate + DL-leucine
-
-
-
-
?
chloroacetyl-DL-norleucine + H2O
chloroacetate + DL-norleucine
-
-
-
-
?
chloroacetyl-DL-serine + H2O
chloroacetate + DL-serine
-
-
-
-
?
chloroacetyl-L-asparagine + H2O
chloroacetate + L-asparagine
-
poor substrate
-
-
?
chloroacetyl-L-aspartate + H2O
chloroacetate + L-aspartate
chloroacetyl-L-glutamic acid + H2O
chloroacetate + L-glutamate
-
-
-
-
?
chloroacetyl-L-leucine + H2O
chloroacetate + L-leucine
-
-
-
-
?
glycyl-L-asparagine + H2O
glycine + L-asparagine
-
-
-
-
?
glycyl-L-aspartic acid + H2O
glycine + L-aspartate
-
-
-
-
?
glycyl-L-glutamic acid + H2O
glycine + L-glutamate
-
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
N-acetyl-L-aspartate + H2O
aspartate + acetate
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
N-acetyl-L-aspartate + H2O
L-aspartate + acetic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
N-acetylalanine + H2O
acetate + alanine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetylarginine + H2O
acetate + arginine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetylasparagine + H2O
acetate + aspartate + NH3
N-acetylaspartate + H2O
acetate + L-aspartate
N-acetylaspartate + H2O
aspartate + acetate
N-acetylaspartate + H2O
L-aspartate + acetate
-
aspartocylase deficiency results in elevated levels of substrate, brain edema and dysmyelination
-
-
?
N-acetylaspartic acid + H2O
aspartate + acetate
N-acetylaspartic acid + H2O
L-asparatate + acetate
N-acetylcysteine + H2O
acetate + cysteine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetylglutamate + H2O
acetate + glutamate
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetylglutamine + H2O
acetate + glutamine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetylleucine + H2O
acetate + leucine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetyllysine + H2O
acetate + lysine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetylmethionine + H2O
acetate + methionine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetylphenylalanine + H2O
acetate + phenylalanine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetylproline + H2O
acetate + proline
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acetyltyrosine + H2O
acetate + tyrosine
poor substrate, 0.1% of the activity towards N-acetyl-aspartate
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
N-carbobenzoxy-L-aspartate + H2O
?
-
-
-
-
?
N-chloroacetyl-L-aspartate + H2O
chloroacetate + L-aspartate
-
-
-
?
N-dichloroacetyl-L-aspartate + H2O
dichloroacetate + L-aspartate
-
-
-
?
N-formyl aspartic acid + H2O
formate + aspartate
-
-
-
-
?
N-formyl-L-aspartate + H2O
formate + L-aspartate
-
-
-
?
N-tert-butoxycarbonyl-L-aspartic acid alpha-benzyl ester + H2O
?
-
-
-
-
?
N-tert-butoxycarbonyl-L-aspartic acid beta-benzyl ester + H2O
?
-
-
-
-
?
N-trifluoroacetyl-L-aspartate + H2O
L-aspartate + trifluoroacetate
-
-
-
-
?
N-trifluoroacetyl-L-aspartate + H2O
trifluoroacetate + L-aspartate
-
-
-
?
additional information
?
-
acetyl-DL-alanine + H2O
acetate + DL-alanine
-
-
-
-
?
acetyl-DL-alanine + H2O
acetate + DL-alanine
-
-
-
-
?
acetyl-DL-methionine + H2O
acetate + methionine
-
-
-
-
?
acetyl-DL-methionine + H2O
acetate + methionine
-
-
-
-
?
acetyl-DL-methionine + H2O
acetate + methionine
-
-
-
-
?
acetyl-L-glutamate + H2O
acetate + glutamate
-
-
-
-
?
acetyl-L-glutamate + H2O
acetate + glutamate
-
-
-
-
?
acetyl-L-leucine + H2O
acetate + leucine
-
-
-
-
?
acetyl-L-leucine + H2O
acetate + leucine
-
-
-
-
?
chloroacetyl-DL-alanine + H2O
chloroacetate + DL-alanine
-
-
-
-
?
chloroacetyl-DL-alanine + H2O
chloroacetate + DL-alanine
-
-
-
-
?
chloroacetyl-L-aspartate + H2O
chloroacetate + L-aspartate
-
-
-
-
?
chloroacetyl-L-aspartate + H2O
chloroacetate + L-aspartate
-
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
-
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
-
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + 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
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
-
-
-
-
?
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
-
-
-
ir
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
-
-
-
-
ir
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
malfunction of the enzyme causes Canavan disease
-
-
?
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
Macaca iris
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
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-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
acetate + L-aspartate
-
-
-
?
N-acetylaspartate + H2O
acetate + L-aspartate
-
-
-
?
N-acetylaspartate + H2O
aspartate + acetate
-
-
-
-
?
N-acetylaspartate + H2O
aspartate + acetate
-
-
-
-
?
N-acetylaspartic acid + H2O
aspartate + acetate
-
-
-
-
?
N-acetylaspartic acid + H2O
aspartate + acetate
-
enzyme mutations cause the Canavan disease and type 2 diabetes
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
-
-
-
?
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
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
-
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
enzyme deficiency, due to mutations of aspartoacylase II, causes the Canavan disease, which is associated with optical neuropathy
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
hydrolysis of N-acetylaspartic acid is important to maintain healthy neurons, the enzyme is upregulated in duodenum of obesity-induced diabetic mice, which might be responsible for diabetic neuropathy, overview
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
-
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
enzyme mutations cause the Canavan disease
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
restoration of deficient enzyme activity by enzyme expression in CNS neurons does not ameliorate motor deficits and demyelination in a model of Canavan disease, which is caused by elevated levels of N-acetylaspartic acid, NAA, neuronal expression of ASPA can compensate for NAA-mediated neuronal hyperexcitation, but not for oligodebdrocyte dysfunciton, overview
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
the enzyme is involved in negative regulation of brain-derived neurotrophic factor, BDNF, and timing of postnatal oligodendrogenesis, overview
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
Macaca iris
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
N-acyl L-aspartic acid + H2O
acetate + L-aspartate
-
-
-
-
?
additional information
?
-
-
the enzyme functions in concert with the plasma membrane transporter NaDC3, that specifically transports N-acetylaspartic acid into the cell
-
-
?
additional information
?
-
-
N-methyl aspartic acid, N-carbamoyl aspartic acid and N-glycyl aspartic acids are no substrates
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
N-acetyl-L-aspartate + H2O
aspartate + acetate
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
N-acetylaspartate + H2O
acetate + L-aspartate
N-acetylaspartate + H2O
aspartate + acetate
N-acetylaspartate + H2O
L-aspartate + acetate
-
aspartocylase deficiency results in elevated levels of substrate, brain edema and dysmyelination
-
-
?
N-acetylaspartic acid + H2O
aspartate + acetate
N-acetylaspartic acid + H2O
L-asparatate + acetate
additional information
?
-
-
the enzyme functions in concert with the plasma membrane transporter NaDC3, that specifically transports N-acetylaspartic acid into the cell
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + L-aspartate
-
-
-
-
?
N-acetyl-L-aspartate + H2O
acetate + 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
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
-
-
-
-
?
N-acetyl-L-aspartate + H2O
L-aspartate + acetate
malfunction of the enzyme causes Canavan disease
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
Macaca iris
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetyl-L-aspartic acid + H2O
acetate + aspartic acid
-
-
-
-
?
N-acetylaspartate + H2O
acetate + L-aspartate
-
-
-
?
N-acetylaspartate + H2O
acetate + L-aspartate
-
-
-
?
N-acetylaspartate + H2O
aspartate + acetate
-
-
-
-
?
N-acetylaspartate + H2O
aspartate + acetate
-
-
-
-
?
N-acetylaspartic acid + H2O
aspartate + acetate
-
-
-
-
?
N-acetylaspartic acid + H2O
aspartate + acetate
-
enzyme mutations cause the Canavan disease and type 2 diabetes
-
-
?
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
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
enzyme deficiency, due to mutations of aspartoacylase II, causes the Canavan disease, which is associated with optical neuropathy
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
hydrolysis of N-acetylaspartic acid is important to maintain healthy neurons, the enzyme is upregulated in duodenum of obesity-induced diabetic mice, which might be responsible for diabetic neuropathy, overview
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
-
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
enzyme mutations cause the Canavan disease
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
-
restoration of deficient enzyme activity by enzyme expression in CNS neurons does not ameliorate motor deficits and demyelination in a model of Canavan disease, which is caused by elevated levels of N-acetylaspartic acid, NAA, neuronal expression of ASPA can compensate for NAA-mediated neuronal hyperexcitation, but not for oligodebdrocyte dysfunciton, overview
-
-
?
N-acetylaspartic acid + H2O
L-asparatate + acetate
the enzyme is involved in negative regulation of brain-derived neurotrophic factor, BDNF, and timing of postnatal oligodendrogenesis, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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A57T
Canavan disease mutation, undetectable enzyme activity
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
D249V
Canavan disease mutation, undetectable enzyme activity
D68A
Canavan disease mutation, undetectable enzyme activity
E178A
undetectable ASPA activity
E178Q
-
site-directed mutagenesis, inactive mutant
E214X
Canavan disease mutation, undetectable enzyme activity
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
G274R
Canavan disease mutation, undetectable enzyme activity
H116G
putative zinc ion binding sites, undetectable ASPA activity
H21G
putative zinc ion binding sites, undetectable ASPA activity
H21P
Canavan disease mutation, undetectable enzyme activity
I143T
Canavan disease mutation, undetectable enzyme activity
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.
M195R
Canavan disease mutation, undetectable enzyme activity
P183H
Canavan disease mutation, undetectable enzyme activity
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
R71N
undetectable ASPA activity
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
Y88X
-
the mutation is associated with Canavan disease
A305E
Canavan disease mutation, undetectable enzyme activity
A305E
10% activity compared to native enzyme form, mutation responsible for the Canavan disease
C152W
Canavan disease mutation, undetectable enzyme activity
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
E178D
10% activity of native enzyme
E24A
no detectable activity
E24A
-
site-directed mutagenesis, inactive mutant
E24D
no detectable activity
E24D
putative zinc ion binding sites, undetectable ASPA activity
E24G
Canavan disease mutation, undetectable enzyme activity
E24G
no protein expression
E24G
putative zinc ion binding sites, undetectable ASPA activity
E285A
Canavan disease mutation, undetectable enzyme activity
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
Canavan disease mutation, undetectable enzyme activity
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
H116A
no detectable activity
H116A
-
site-directed mutagenesis, inactive mutant
H21A
no detectable activity
H21A
-
site-directed mutagenesis, inactive mutant
K213E
Canavan disease mutation, undetectable enzyme activity
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
R63N
undetectable ASPA activity
R63N
the mutation results in undetectable activity
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
additional information
-
knockout of aspartoacylase activity leads to sponginess and loss of white matter in Canavan disease, and to increased expression/activity of cdk2, NCAM, nestin, vimentin, and NG2. Differentiation of neuronal progenitor cells is arrested, phenotype, overview
additional information
Gata6flox/flox mice on a mixed 129S1/SvImJ and CD-1 background are bred with Lyz2-Cre+/- on a C57BL/6 background to yield Cre+/-Gata6-Mac mice and Cre-/- Gata6flox/flox littermate control mice. Nur7 mice bearing mutant Aspa alleles are on a C57BL/6J background and compared with C57BL/6J mice
additional information
-
restoration of deficient enzyme activity in CNS neurons does not ameliorate motor deficits and demyelination in a model of Canavan disease, which is caused by elevated levels of N-acetylaspartic acid, NAA, neuronal expression of ASPA can compensate for NAA-mediated neuronal hyperexcitation, but not for oligodebdrocyte dysfunciton, phenotypes, overview
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Mutational analysis of aspartoacylase: implications for Canavan disease
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980
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Homo sapiens (P45381)
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Mus musculus
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Homo sapiens (P45381), Homo sapiens
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Homo sapiens
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Homo sapiens (P45381), Homo sapiens
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Aspartoacylase catalytic deficiency as the cause of Canavan disease: a structural perspective
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53
4970-4978
2014
Homo sapiens (P45381)
brenda
Gautier, E.; Ivanov, S.; Williams, J.; Huang, S.; Marcelin, G.; Fairfax, K.; Wang, P.; Francis, J.; Leone, P.; Wilson, D.; Artyomov, M.; Pearce, E.; Randolph, G.
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Mus musculus (Q8R3P0)
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Mol. Genet. Metab.
113
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Homo sapiens (P45381)
brenda
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Homo sapiens (P45381), Homo sapiens
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Allosteric control of N-acetyl-aspartate hydrolysis by the Y231C and F295S mutants of human aspartoacylase
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59
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2019
Homo sapiens (P45381), Homo sapiens
brenda
Khrenova, M.G.; Kots, E.D.; Varfolomeev, S.D.; Lushchekina, S.V.; Nemukhin, A.V.
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2017
Homo sapiens (P45381), Homo sapiens
brenda
George Priya Doss, C.; Zayed, H.
Comparative computational assessment of the pathogenicity of mutations in the aspartoacylase enzyme
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32
2105-2118
2017
Homo sapiens (P45381), Homo sapiens
brenda
Kots, E.; Khrenova, M.; Lushchekina, S.; Nemukhin, A.
Mechanisms of the aspartoacylase catalytic activity regulation according to the computer modeling results
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73
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2018
Homo sapiens (P45381)
-
brenda
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)
-
brenda