3.5.1.15: aspartoacylase
This is an abbreviated version!
For detailed information about aspartoacylase, go to the full flat file.
Word Map on EC 3.5.1.15
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3.5.1.15
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canavan
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n-acetylaspartate
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leukodystrophy
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matter
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myelin
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oligodendrocyte
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spongy
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n-acetyl-l-aspartate
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spongiform
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macrocephaly
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tremor
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ashkenazi
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jewish
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non-jewish
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dysmyelination
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nutrition
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medicine
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pharmacology
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n-acetylaspartylglutamate
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triacetate
- 3.5.1.15
- canavan
- n-acetylaspartate
- leukodystrophy
- matter
- myelin
- oligodendrocyte
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spongy
- n-acetyl-l-aspartate
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spongiform
- macrocephaly
- tremor
-
ashkenazi
-
jewish
-
non-jewish
-
dysmyelination
- nutrition
- medicine
- pharmacology
- n-acetylaspartylglutamate
- triacetate
Reaction
Synonyms
acetyl-aspartic deaminase, Acylase II, aminoacylase 2, Aminoacylase II, aminoacylase-2, ASPA, aspartic acid acylase, Aspartoacylase, aspartoacylase II, hASPA, human ASPA, More, murine aspartoacylase, N-acetyl-aspartate deacetylase, N-Acetyl-L-aspartate amidohydrolase, N-Acetylaspartate amidohydrolase, N-acetylaspartocylase, NAA acylase
ECTree
3.5.1.15 aspartoacylaseAdvanced search results
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results (Engineering
Engineering on EC 3.5.1.15 - aspartoacylase
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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
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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
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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
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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
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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
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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
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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
