Literature summary extracted from

Kots, E.; Khrenova, M.; Nemukhin, A.; Varfolomeev, S.
Aspartoacylase A central nervous system enzyme. Structure, catalytic activity and regulation mechanisms (2019), Russ. Chem. Rev., 88, 1-26 .

No PubMed abstract available

Protein Variants

EC Number	Protein Variants	Comment	Organism
3.5.1.15	A305E	10% activity compared to native enzyme form, mutation responsible for the Canavan disease	Homo sapiens
3.5.1.15	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	Homo sapiens
3.5.1.15	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	Homo sapiens
3.5.1.15	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	Homo sapiens
3.5.1.15	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	Homo sapiens
3.5.1.15	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	Homo sapiens
3.5.1.15	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	Homo sapiens
3.5.1.15	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	Homo sapiens

Inhibitors

EC Number	Inhibitors	Comment	Organism	Structure
3.5.1.15	N-acetyl-L-aspartate	substrate inhibition at high concentration	Homo sapiens

KM Value [mM]

EC Number	KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
3.5.1.15	0.21	-	N-trifluoroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	0.23	-	N-dichloroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	0.36	-	N-acetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	0.59	-	N-Chloroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	0.95	-	N-formyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens

Metals/Ions

EC Number	Metals/Ions	Comment	Organism	Structure
3.5.1.15	Zn2+	zinc-dependent enzyme. Zn2+ coordination region: His21, Glu24 and His116	Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number	Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
3.5.1.15	N-acetyl-L-aspartate + H2O	Homo sapiens	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	acetate + L-aspartate	-	?

Organism

EC Number	Organism	UniProt	Comment	Textmining
3.5.1.15	Homo sapiens	P45381	-	-

Substrates and Products (Substrate)

EC Number	Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
3.5.1.15	N-acetyl-L-aspartate + H2O	-	Homo sapiens	acetate + L-aspartate	-	?
3.5.1.15	N-acetyl-L-aspartate + H2O	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	Homo sapiens	acetate + L-aspartate	-	?
3.5.1.15	N-chloroacetyl-L-aspartate + H2O	-	Homo sapiens	chloroacetate + L-aspartate	-	?
3.5.1.15	N-dichloroacetyl-L-aspartate + H2O	-	Homo sapiens	dichloroacetate + L-aspartate	-	?
3.5.1.15	N-formyl-L-aspartate + H2O	-	Homo sapiens	formate + L-aspartate	-	?
3.5.1.15	N-trifluoroacetyl-L-aspartate + H2O	-	Homo sapiens	trifluoroacetate + L-aspartate	-	?

Subunits

EC Number	Subunits	Comment	Organism
3.5.1.15	homodimer	-	Homo sapiens

Turnover Number [1/s]

EC Number	Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism	Structure
3.5.1.15	0.083	-	N-acetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	0.25	-	N-formyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	0.62	-	N-Chloroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	0.77	-	N-dichloroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	1.2	-	N-trifluoroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens

General Information

EC Number	General Information	Comment	Organism
3.5.1.15	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	Homo sapiens
3.5.1.15	physiological function	aspartoacylase is a key enzyme in the human central nervous system	Homo sapiens

kcat/KM [mM/s]

EC Number	kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism	Structure
3.5.1.15	0.23	-	N-acetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	0.26	-	N-formyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	1	-	N-Chloroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	3.4	-	N-dichloroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens
3.5.1.15	5.8	-	N-trifluoroacetyl-L-aspartate	pH and temperature not specified in the publication	Homo sapiens

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Release 2023.1 (January 2023)