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Information on EC 2.3.1.17 - aspartate N-acetyltransferase and Organism(s) Homo sapiens and UniProt Accession Q8N9F0
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EC Tree
2.3.1.17 aspartate N-acetyltransferaseSpecify your search results
Word Map
- 2.3.1.17
- n-acetylaspartate
- canavan
- aspartoacylase
- n-acetyl-l-aspartate
- oligodendrocytes
- leukodystrophy
-
8-like
- methamphetamine
-
spongiform
-
lipolysis
- n-acetylaspartylglutamate
- naags
-
cholinergic
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
nat8l, aspartate n-acetyltransferase, l-aspartate n-acetyltransferase, aspartate acetyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetyltransferase, aspartate
-
-
-
-
aspartate acetyltransferase
-
-
-
-
aspartic acetylase
-
-
-
-
L-aspartate N-acetyltransferase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:L-aspartate N-acetyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
9029-99-6
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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
acetyl-CoA + 3-methyl-L-aspartate
CoA + N-acetyl-3-methyl-L-aspartate
-
-
-
?
acetyl-CoA + L-glutamate
CoA + N-acetyl-L-glutamate
reaction of EC 2.3.1.1
-
-
?
acetyl-CoA + L-glutamate
CoA + N-acetyl-L-glutamic acid
less than 1% of the activity with L-aspartate
-
-
?
acetyl-CoA + L-aspartate
CoA + N-acetyl-L-aspartic acid
-
-
-
?
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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-(2,6-dibromo-4-carboxybenzyl)-N-carboxyethyl-3,4-dicarboxybenzylamine
-
N-(2,6-dichloro-4-carboxybenzyl)-N-carboxyethyl-3,4-dicarboxybenzylamine
-
N-acetyl-(dimethyl)aspartyl-conjugated CoA
coenzyme A coupled to methylated N-acetyl aspartate, bisubstrate inhibitor
N-acetylaspartyl-conjugated CoA
coenzyme A coupled to N-acetyl aspartate, bisubstrate inhibitor
N-methyl-N-nonanoyl-beta-D-glucosylamine
Mega-9, high inhibition at CMC concentration
N-propionyl-(dimethyl)aspartyl-conjugated CoA
coenzyme A coupled to N-propionyl aspartate, bisubstrate inhibitor
N-[((2-[(tert-butoxycarbonyl)amino]ethyl)sulfanyl)acetyl]-L-aspartic acid
truncated bisubstrate analog
sodium 2-[(tert-butoxycarbonyl)amino]-3-[(2-([(1S)-1,2-dicarboxyethyl]amino)-2-oxoethyl)sulfanyl]propanoate
truncated bisubstrate analog
sodium 3-[(2-([(1S)-1,2-dicarboxyethyl]amino)-2-oxoethyl)sulfanyl]-2-([(trifluoromethoxy)carbonyl]amino)propanoate
truncated bisubstrate analog
additional information
effect of different detergents on the enzyme activity: non-ionic detergents such as Triton X-100 are less disruptive to protein structures than ionic detergents such as SDS, detergents such as C12E8, Tween 20 and several maltosides caused minimal disruption of the enzyme, with greater than 50% residual activity after incubation with CMC levels of each of these detergents. In contrast, significant loss of activity is observed upon incubation with C8 detergents, cymal5, octylglucoside and some shorter chain polymaleic anhydride (pmal) detergents. Ionic detergent SDS and a zwitterionic detergent lauryldimethylamine-N-oxide cause nearly complete loss of catalytic activity
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additional information
-
effect of different detergents on the enzyme activity: non-ionic detergents such as Triton X-100 are less disruptive to protein structures than ionic detergents such as SDS, detergents such as C12E8, Tween 20 and several maltosides caused minimal disruption of the enzyme, with greater than 50% residual activity after incubation with CMC levels of each of these detergents. In contrast, significant loss of activity is observed upon incubation with C8 detergents, cymal5, octylglucoside and some shorter chain polymaleic anhydride (pmal) detergents. Ionic detergent SDS and a zwitterionic detergent lauryldimethylamine-N-oxide cause nearly complete loss of catalytic activity
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Methamphetamine
maximum increase in activity in SH-SY5Y cells is found at 1 microM methamphetamine at 24 h, increase in activity is about 2fold
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.92
2,3-diaminosuccinate
pH 7.4, temperature not specified in the publication
0.36
3-methyl-L-aspartate
pH 7.4, temperature not specified in the publication
additional information
additional information
Michaelis-Menten kinetics
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.035
2,3-diaminosuccinate
pH 7.4, temperature not specified in the publication
0.0018
3-methyl-L-aspartate
pH 7.4, temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.031
(2S)-2-(3-phenylpropanamido)butanedioic acid
pH 7.4, temperature not specified in the publication
0.038
(2S)-2-(3-phenylpropanamido)pentanedioic acid
pH 7.4, temperature not specified in the publication
0.017
(2S)-2-[[(benzyloxy)carbonyl]amino]butanedioic acid
pH 7.4, temperature not specified in the publication
0.012
(2S)-2-[[(benzyloxy)carbonyl]amino]pentanedioic acid
pH 7.4, temperature not specified in the publication
0.0006
4-aminomethyl(N-carboethyl,N-4-carboxy-2,6-dichlorobenzyl)phthalate
pH 7.4, temperature not specified in the publication
2.3
adenosine 3',5'-monophosphate
pH not specified in the publication, temperature not specified in the publication
1.1
adenosine 5'-diphosphate
pH not specified in the publication, temperature not specified in the publication
4
adenosine 5'-monophosphate
pH not specified in the publication, temperature not specified in the publication
0.96
adenosine 5'-triphosphate
pH not specified in the publication, temperature not specified in the publication
0.00077
N-(2,6-dibromo-4-carboxybenzyl)-N-carboxyethyl-3,4-dicarboxybenzylamine
pH 7.4, temperature not specified in the publication
0.00061
N-(2,6-dichloro-4-carboxybenzyl)-N-carboxyethyl-3,4-dicarboxybenzylamine
pH 7.4, temperature not specified in the publication
0.018
N-acetyl-(dimethyl)aspartyl-conjugated CoA
pH not specified in the publication, temperature not specified in the publication
1.6
N-acetylaspartate
pH not specified in the publication, temperature not specified in the publication
0.000275
N-acetylaspartyl-conjugated CoA
pH not specified in the publication, temperature not specified in the publication
0.017
N-carbobenzyloxy-L-aspartic acid
pH 7.4, temperature not specified in the publication
0.012
N-carbobenzyloxy-L-glutamic acid
pH 7.4, temperature not specified in the publication
0.2
N-chloroacetylaspartate
pH not specified in the publication, temperature not specified in the publication
0.000048
N-propionyl-(dimethyl)aspartyl-conjugated CoA
pH not specified in the publication, temperature not specified in the publication
2.1
N-[((2-[(tert-butoxycarbonyl)amino]ethyl)sulfanyl)acetyl]-L-aspartic acid
pH not specified in the publication, temperature not specified in the publication
0.87
sodium 2-[(tert-butoxycarbonyl)amino]-3-[(2-([(1S)-1,2-dicarboxyethyl]amino)-2-oxoethyl)sulfanyl]propanoate
pH not specified in the publication, temperature not specified in the publication
1.03
sodium 3-[(2-([(1S)-1,2-dicarboxyethyl]amino)-2-oxoethyl)sulfanyl]-2-([(trifluoromethoxy)carbonyl]amino)propanoate
pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70
recombinant enzyme, pH 7.4, temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9.5
the enzymatic activity decreases at pH values below pH 7.5. A fit of the Vmax/Km data to a model which assumes that the protonation of a single group leads to loss of activity results in a pK value of 6.8 for a group that must be ionized for the enzyme to remain catalytically active. By contrast, the Vmax profile does not show substantial changes across the pH range
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
exclusively associated with the endoplasmic reticulum. the membrane region comprises alpha-helices and the catalytic site is in the cytosol. The membrane region, i.e. region 4, is necessary and sufficient to target isoform NAT8L to the endoplasmic reticulum
membrane-associated, the enzyme contains a membrane anchor region
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
Canavan disease is a fatal, neurological disease that is caused by an interruption in the metabolism of a critical amino acid, N-acetyl-L-aspartic acid. Defects at multiple locations in the aspA gene that codes for aspartoacylase, EC 3.5.1.15, lead to mutant forms of this enzyme that are either not expressed or rapidly degraded, or have significantly impaired catalytic activity, resulting in N-acetyl-L-aspartic acid accumulation. A second gene knock-out in the Nat8l gene which codes for aspartate N-acetyltransferase, the enzyme that synthesizes N-acetyl-L-aspartic acid, reverses these adverse effects, leading to normal myelination and a decrease in Canavan disease symptoms
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). NAT8L_HUMAN
302
1
32837
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
33900
x * 56000-60000, recombinant MBP-His-tagged enzyme without membrane anchor, SDS-PAGE, x * 33900, recombinant His-tagged enzyme without membrane anchor, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 56000-60000, recombinant MBP-His-tagged enzyme without membrane anchor, SDS-PAGE, x * 33900, recombinant His-tagged enzyme without membrane anchor, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular modeling of the active site shows that only the amino acid aspartate, but not glutamate, can fit into the active site pocket
purified recombinant His-tagged truncated enzyme, X-ray diffraction structure determination and analysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C128A
mutation in region 4, 94% of wild-type expression, 88% of wild-type activity
C139A
mutation in region 4, 70% of wild-type expression, 126% of wild-type activity
D168A
mutation in region 5, 46% of wild-type expression, no residual activity
D168E
mutation in region 5, 63% of wild-type expression, 7% of wild-type activity
E101A
mutation in region 3, 97% of wild-type expression, 42% of wild-type activity
E101D
mutation in region 3, 61% of wild-type expression, 99% of wild-type activity
P142A
mutation in region 4, 113% of wild-type expression, 116% of wild-type activity
R133A
mutation in region 4, 78% of wild-type expression, 64% of wild-type activity
R133K
mutation in region 4, 69% of wild-type expression, 89% of wild-type activity
R220A
mutation in region 5, 101% of wild-type expression, 14% of wild-type activity
R220K
mutation in region 5, 104% of wild-type expression, 25% of wild-type activity
R81A
mutation in region 3, 57% of wild-type expression, 37% of wild-type activity
R81K
mutation in region 3, 90% of wild-type expression, 82% of wild-type activity
S132F/R133F
mutation in region 4, 92% of wild-type expression, 41% of wild-type activity
additional information
transfection of truncated forms of isoform NAT8L into HEK-293T cells indicates that the 68 N-terminal residues, i.e. regions 1 and 2, have no importance for the catalytic activity and the subcellular localization of the enzyme. The membrane region, i.e. region 4, is necessary and sufficient to target isoform NAT8L to the endoplasmic reticulum
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant functional and soluble dual His- and MBP-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and amylose affinity chromatography, MBP tag cleavage by 3C protease, method evaluation
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene nat8l, sequence comparisons, subcloning of the genes for thioredoxin (TRX), glutathione S-transferase (GST) or maltose binding protein (MBP), followed by a linker region (21-68-amino acids) containing various cleavage site sequences, and then connected to the N-terminal of the nat8l gene, without the membrane anchor, recombinant functional and soluble expression of the dual affinity tagged enzyme as MBP-fusion protein in Escherichia coli strain BL21(DE3), method evaluation
overexpressed both as native and as fusion protein with a His6 tag at the C- or the N-terminus in human embryonic kidney-293 cells expressing the large T-antigen of simian virus 40 (HEK-293T cells)
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
patients with high levels of tumoral N-acetyl-L-aspartate and its biosynthetic enzyme, aspartate N-acetyltransferase (NAT8L), have worse overall survival than patients with low levels of N-acetyl-L-aspartate and NAT8L. The overall survival duration of patients with higher-than-median N-acetyl-L-aspartate levels (3.6 years) is lower than that of patients with lower-than-median N-acetyl-L-aspartate levels (5.1 years). High NAT8L gene expression in other cancers (melanoma, renal cell, breast, colon, and uterine cancers) is associated with worse overall survival. NAT8L silencing reduces cancer cell viability and proliferation. In orthotopic mouse models (ovarian cancer and melanoma), NAT8L silencing reduces tumor growth statistically significantly
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Moreno, A.; Ross, B.D.; Bluml, S.
Direct determination of the N-acetyl-L-aspartate synthesis rate in the human brain by (13)C MRS and [1-(13)C]glucose infusion
J. Neurochem.
77
347-350
2001
Homo sapiens
Wiame, E.; Tyteca, D.; Pierrot, N.; Collard, F.; Amyere, M.; Noel, G.; Desmedt, J.; Nassogne, M.C.; Vikkula, M.; Octave, J.N.; Vincent, M.F.; Courtoy, P.J.; Boltshauser, E.; van Schaftingen, E.
Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia
Biochem. J.
425
127-136
2010
Danio rerio, Homo sapiens (Q8N9F0), Homo sapiens, Mus musculus
Tahay, G.; Wiame, E.; Tyteca, D.; Courtoy, P.J.; Van Schaftingen, E.
Determinants of the enzymatic activity and the subcellular localization of aspartate N-acetyltransferase
Biochem. J.
441
105-112
2012
Homo sapiens (Q8N9F0)
Ariyannur, P.S.; Moffett, J.R.; Manickam, P.; Pattabiraman, N.; Arun, P.; Nitta, A.; Nabeshima, T.; Madhavarao, C.N.; Namboodiri, A.M.
Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: implications for specialized acetyl coenzyme A metabolism in the CNS
Brain Res.
1335
1-13
2010
Homo sapiens (Q8N9F0), Homo sapiens, Mus musculus (Q3UGX3)
Wang, Q.; Zhao, M.; Parungao, G.G.; Viola, R.E.
Purification and characterization of aspartate N-acetyltransferase: a critical enzyme in brain metabolism
Protein Expr. Purif.
119
11-18
2016
Homo sapiens (Q8N9F0), Homo sapiens
Thangavelu, B.; Mutthamsetty, V.; Wang, Q.; Viola, R.E.
Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease
Bioorg. Med. Chem.
25
870-885
2017
Homo sapiens (Q8N9F0), Homo sapiens
Mutthamsetty, V.; Dahal, G.P.; Wang, Q.; Viola, R.E.
Development of bisubstrate analog inhibitors of aspartate N-acetyltransferase, a critical brain enzyme
Chem. Biol. Drug Des.
95
48-57
2020
Homo sapiens (Q8N9F0), Homo sapiens
Zand, B.; Previs, R.A.; Zacharias, N.M.; Rupaimoole, R.; Mitamura, T.; Nagaraja, A.S.; Guindani, M.; Dalton, H.J.; Yang, L.; Baddour, J.; Achreja, A.; Hu, W.; Pecot, C.V.; Ivan, C.; Wu, S.Y.; McCullough, C.R.; Gharpure, K.M.; Shoshan, E.; Pradeep, S.; Mangala, L.S.; Rodriguez-Aguayo, C.; Wang, Y.; Nick, A.M.
Role of increased N-acetylaspartate levels in cancer
J. Natl. Cancer Inst.
108
djv426
2016
Homo sapiens (Q8N9F0), Homo sapiens
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