2.3.1.5: arylamine N-acetyltransferase
This is an abbreviated version!
For detailed information about arylamine N-acetyltransferase, go to the full flat file.
Word Map on EC 2.3.1.5
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2.3.1.5
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pineal
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melatonin
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rhythm
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circadian
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n-acetylation
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retina
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2-aminofluorene
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night
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p-aminobenzoic
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nocturnal
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arylalkylamine
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n-acetylserotonin
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hydrazine
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medicine
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diurnal
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isoniazid
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light-dark
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aa-nat
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paba
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pinealocytes
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nighttime
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hydroxyindole-o-methyltransferase
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sulfamethazine
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hiomt
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accoa
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xenobiotic-metabolizing
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monomorphic
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daytime
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quinpirole
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tryptamine
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anti-tubercular
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pharmacology
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sulpiride
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light-exposed
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analysis
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molecular biology
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n-hydroxylated
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drug development
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midnight
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p-aminosalicylic
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o-acetyltransferase
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n-hydroxyarylamine
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spiroperidol
- 2.3.1.5
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pineal
- melatonin
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rhythm
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circadian
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n-acetylation
- retina
- 2-aminofluorene
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night
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p-aminobenzoic
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nocturnal
- arylalkylamine
- n-acetylserotonin
- hydrazine
- medicine
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diurnal
- isoniazid
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light-dark
- aa-nat
- paba
- pinealocytes
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nighttime
- hydroxyindole-o-methyltransferase
- sulfamethazine
- hiomt
- accoa
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xenobiotic-metabolizing
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monomorphic
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daytime
- quinpirole
- tryptamine
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anti-tubercular
- pharmacology
- sulpiride
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light-exposed
- analysis
- molecular biology
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n-hydroxylated
- drug development
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midnight
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p-aminosalicylic
- o-acetyltransferase
- n-hydroxyarylamine
-
spiroperidol
Reaction
Synonyms
(BACAN)NAT3, (MYCAB)NAT1, 2-naphthylamine N-acetyltransferase, 4-aminobiphenyl N-acetyltransferase, ABW01_24350, acetyl CoA-arylamine N-acetyltransferase, acetyltransferase, 2-naphthylamine N-, acetyltransferase, 4-aminobiphenyl, acetyltransferase, arylamine, acetyltransferase, p-aminosalicylate N-, acetyltransferase, procainamide N-, acetyltransferase, serotonin N-, arylamine acetylase, arylamine acetyltransferase, arylamine N-acetyl transferase, arylamine N-acetyltransferase, arylamine N-acetyltransferase 1, arylamine N-acetyltransferase 2, arylamine N-acetyltransferase C, arylamine N-acetyltransferase I, arylamine N-acetyltransferase type 1, arylamine N-acetyltransferase type 2, arylamine N-acetyltransferase type I, arylamine-N-acetyltransferase 1, BanatA, BanatB, BanatC, beta-naphthylamine N-acetyltransferase, indoleamine N-acetyltransferase, MlNAT1, MMNAT, More, MSNAT, N-acetyltransferase, N-acetyltransferase a, N-acetyltransferase b, N-acetyltransferase type 2, N-hydroxyarylamine O-acetyltransferase, NAT, NAT 1, NAT-a, NAT-b, NAT1, NAT2, NAT2*1, NAT2*2, NAT3, NAT31, NfNAT, p-aminosalicylate N-acetyltransferase, PANAT, rhesus NAT2, serotonin acetyltransferase, serotonin N-acetyltransferase, STNAT, TBNAT, Tpau_4046, UDP-2-acetamido-3-amino-2,3-dideoxy-D-glucuronic acid 3-N-acetyltransferase, UDP-D-Glc(2NAc3N)A 3-N-acetyltransferase, WbpD
ECTree
2.3.1.5 arylamine N-acetyltransferaseAdvanced search results
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results (Engineering
Engineering on EC 2.3.1.5 - arylamine N-acetyltransferase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C69A
Y38F
E123D
-
the catalytic efficiency is 1.6-4.4 times higher than that of the wild type enzyme
A434C
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
A752T
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
A803G
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
C190T
C559T
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
C68G
C97T
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
D122N
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR
E167K
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR. Reduction in maximum activity
E203D
-
609T, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
E264K
E8G
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
F125S
F192Y
site-directed mutagenesis, the NAT2 mutant shows highly reduced activity compared to the wild-type enzyme
G191A
G286E
G364A
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
G499A
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
G560A
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
G590A
G857A
H43R
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
I114T
I238T
-
activity with 2-aminofluorene is about 30% of the wild-type activity, the KM-value for 2-aminofluorene is 1.3fold higher than the wild-type value
I32V
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
K100E
-
the mutation significantly increases the Ka value for acetyl-CoA without changing the Kb value for the acetyl acceptor 4-aminobenzoate
K100L
-
the mutation significantly increases the Ka value for acetyl-CoA without changing the Kb value for the acetyl acceptor 4-aminobenzoate
K100Q
mutation decreases the potency of ATP as an inhibitor of NAT1. The Hill coefficient increases twofold
K100R
K13R
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
K141E
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
K185N
-
activity with 2-aminofluorene is about 35% of the wild-type activity, the KM-value for 2-aminofluorene is 1.5fold higher than the wild-type value
K268R
K282T
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR
L135V
-
403G, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
L137F
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR
L239F
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
L24I
-
70A, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
L69P
site-directed mutagenesis, the NAT2 mutant shows highly reduced activity compared to the wild-type enzyme
L74P
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
N172I
-
activity with 2-aminofluorene is about 20% of the wild-type activity, the KM-value for 2-aminofluorene is 3.6fold higher than the wild-type value
N245I
NAT2*12A.U4
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*13.U1
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*4.U1
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*4.U2
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*4.U3
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*4.U5
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*4.U6
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*4.U7
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*5B.U1
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polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*5B.U4
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*6A.U1
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*7B.U2
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
NAT2*7B.U3
-
polymorphism, proposed new nomenclature composed of haplotype in the promoter region and conventional NAT2 haplotype in the coding region
P228L
-
683T, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
Q133R
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
Q145P
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR. Reduction in both N- and O-acetyltransferase catalytic activitiy
R127S
-
mutant shows a 42fold decreased affinity for the NAT1-selective substrate p-aminobenzoic acid
R197Q
R242M
single nucleotide variant, identified within a South African mixed ancestry population, displays a similar profile to the published variant, I263V (proposed fast acetylator), and the wild-type protein structure
R64Q
R64W
S102C
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
S125F/S127R/S129Y
-
mutation of all three Ser residues 125, 127 and 129 to those normally present in NAT1 is required to produce the low affinity for sulfamethazine approximating that of native NAT1
T207S
-
activity with 2-aminofluorene is slightly higher than wild-type activity
T250P
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
T341C
V231G
V280M
-
838A, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
W77R
-
activity with 2-aminofluorene is about 25% of the wild-type activity, the KM-value for 2-aminofluorene is 1.3fold higher than the wild-type value
Y190C
site-directed mutagenesis, the NAT2 mutant shows highly reduced activity compared to the wild-type enzyme
Y190F
site-directed mutagenesis, the NAT2 mutant shows reduced activity compared to the wild-type enzyme
D115Y
non-synonymous single nucleotide variation, about 68% decrease in stability, about 82% decrease in activity
E155Q
non-synonymous single nucleotide variation, about 62% decrease in stability, about 22% decrease in activity
F175L
non-synonymous single nucleotide variation, about 50% decrease in stability, about 82% decrease in activity
G51A
non-synonymous single nucleotide variation, about 60% decrease in stability, about 45% decrease in activity
L89F
non-synonymous single nucleotide variation, about 56% decrease in stability, about 69% decrease in activity
L89F/D115Y
non-synonymous single nucleotide variation, about 95% decrease in stability, less about 95% decrease in activity
M82V
non-synonymous single nucleotide variation, about 68% decrease in stability, about 32% decrease in activity
R187Q
non-synonymous single nucleotide variation, about 27% decrease in stability, about 73% decrease in activity
recombinant (MACMU)NAT2 protein
analysed for the ability to acetylate NAT substrates and bind anti-NAT antibodies
V231I
polymorphic allele Nat2*2 found in rhesus macaque, differentiated by one nonsynonymous G691A polymorphism, resulting in a Val231Ile substitution. Mutant shows differences in activity with most substrates (pmol/min/luminescence unit): 183 (p-anisidine), 4 (procainamide), 3 (sulphamethazine), 11 (5-aminosalicylate), 3 (p-aminobenzoic acid)
H107N
site-directed mutagenesis, no expression in Escherichia coli cells possible
H107Q
site-directed mutagenesis, no expression in Escherichia coli cells possible, insoluble inactive enzyme
R64W
F42W
the mutant displays enzymatic properties similar to those of the wild type enzyme
G129A
G129I
G129P
G129S
G129T
G129V
I95T
-
in liver of homozygous animals, 90% reduction in activity with substrate isoniazid
R99I
-
Mus musculus A/J slow acetylating strain harbours a R99I mutation in the Nat2 gene, causing instability and degradation of the mutant protein
E26D/L82M
-
in Mus spretus mice, slow acetylation is associated with an unstable Nat2 protein in which there are two amino acid changes Glu26Asp and Leu82Met
M209T
-
replacement of residue M209 with the corresponding residue from Mycobacterium tuberculosis enzyme. Activities against several substrates similar to wild-type, with similar overall trends
Y71F
-
replacement of residue Y71 with the corresponding residue from Mycobacterium tuberculosis enzyme. Activities against several substrates similar to wild-type, with similar overall trends
G207R
-
mutation found in clinically isolated strains of Mycobacterium tuberculosis, resulting in a NAT enzyme with very poor activity
K136A
-
site-directed mutagenesis, the mutant can only partially complement the wbpD knockout mutant strain, and shows also reduced stabilizing effects of acetyl-CoA on the mutant enzyme, while a K136R mutation shows no discernible effect on complementation of the wbpD mutant or the stabilizing effects of acetyl-CoA on the purified mutant protein
K136R
-
site-directed mutagenesis, partial complementation of the knockout mutant strain
K58A
-
site-directed mutagenesis, complete complementation of the knockout mutant strain to wild-type levels
K58R
-
site-directed mutagenesis, complete complementation of the knockout mutant strain to wild-type levels
Q60A
-
site-directed mutagenesis, partial complementation of the knockout mutant strain
Q60N
-
site-directed mutagenesis, partial complementation of the knockout mutant strain
additional information
C69A
A0A0F7R932, Q81PT0, Q81R98
BanatC inactive mutant, replacement of the catalytic cysteine residue
C69A
A0A0F7R932, Q81PT0, Q81R98
mutant devoid of NAT activity. Expression of the C69A mutant in Escherichia coli does not afford higher-than-normal resistance to sulfonamide antibiotic sulfamethoxazole in the recombinant bacteria
Y38F
-
crystallization studies are carried out with mutant Y38F since it leads to a decreased proteolysis when recombinantly expressed in Escherichia coli and enzymatic properties are shown to be identical. Crystals belong to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 53.70, c = 172.40 A, and diffract to 1.95 A resolution on a synchrotron source
Y38F
-
whereas wild-type BanatC proves difficult to crystallize, the mutant displaying the same enzymatic characterisics as the wild-type is found to crystallize and to diffract
C190T
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
C68G
-
the sulfhydryl-group of a single cysteine residue participates in the mechanism of acetyl transfer from acetyl CoA to acceptor amine substrate via a two step, substituted-enzyme (ping pong, bi bi) reaction mechanism: Site-directed mutagenesis studies using recombinant human NAT2 shows that only Cys with Gly at position 68 completely abolishes catalytic function, establishing Cys68 as the key sulfhydryl-containing residue in the catalytic mechanism
E264K
single nucleotide variant, identified within a South African mixed ancestry population, substitution occupies less conformational clusters of folded states as compared to the wild-type and is destabilizing
E264K
single nucleotide variant, identified within a South African mixed ancestry population. Less thermodynamically stable protein structure is predicted
F125S
-
mutant produces a 220fold increased affinity for the NAT2-selective substrate sulfamethazine, Km (sulfamethazine): 0.02 mM
G191A
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
G286E
-
857A, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
G286E
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR. Reduction in maximum activity
G590A
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
G857A
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
I114T
-
341C, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
I114T
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR. Reduction in both N- and O-acetyltransferase catalytic activitiy
K100R
-
the mutation significantly decreases the Ka value for acetyl-CoA without changing the Kb value for the acetyl acceptor 4-aminobenzoate
K100R
mutation decreases the potency of ATP as an inhibitor of NAT1. The Hill coefficient increases threefold
K268R
-
803G, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
K268R
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR
N245I
-
activity with 2-aminofluorene is about 85% of the wild-type activity, the KM-value for 2-aminofluorene is 1.3fold higher than the wild-type value
N245I
single nucleotide variant, identified within a South African mixed ancestry population. Thermodynamically stabilizing effect structure is predicted and affecting NAT1 protein function
R197Q
-
590A, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
R197Q
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR. Reduction in both N- and O-acetyltransferase catalytic activitiy. Reduction in maximum activity
R64Q
structural basis of the effects of the common genetic polymorphism on NAT2 activity, enzyme and active site structure analysis, phenotype, overview
R64Q
-
191A, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect missense
R64Q
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR. Reduction in both N- and O-acetyltransferase catalytic activitiy
R64W
naturally occuring polymorphism in gene NAT1, the R64W mutation also causes constitutive ubiquitinylation and NAT1 to aggregate in cultured cells, does not interfere with NAT catalysis in vitro, overall protein structure and thermostability are not compromised
R64W
single nucleotide polymorphism, evaluation of functional effect based on crystal strucutre, PDB 2PFR. Reduction in both N- and O-acetyltransferase catalytic activitiy
T341C
single nucleotide polymorphism (SNP) found in human, resulting in a decreased activity of enzyme
V231G
single nucleotide variant, identified within a South African mixed ancestry population, substitution occupies less conformational clusters of folded states as compared to the wild-type and is destabilizing
V231G
single nucleotide variant, identified within a South African mixed ancestry population. Less thermodynamically stable protein structure and is predicted, and affecting NAT1 protein function
R64W
naturally occuring polymorphism in gene NAT2, the R64W mutation also causes constitutive ubiquitinylation and NAT2 to aggregate in cultured cells, does not interfere with NAT catalysis in vitro, overall protein structure and thermostability are not compromised
R64W
-
change from arginine to tryptophane at residue 64 seriously affects protein stability. Mutant is shown to cluster in cytosolic aggresomes and is rapidly ubiquitinylated and degraded
G129A
-
final protein yield similar to wild-type: approximately 30 mg. Enzymatic activity: 4.758 micromol/min/mg, Km (mM): 0.184 (substrate: p-aminosalicylic acid)
G129A
-
mutation of the conserved glycine residue in the active-site P-loop
G129I
-
mutation of the conserved glycine residue in the active-site P-loop
G129I
-
only low levels of protein production, NAT activity: 0.034 micromol/min/mg
G129I
-
only small amount of NAT protein, final protein yield: 0.75-0.5 mg of protein. Enzymatic activity: very low, not accurately measurable
G129P
-
mutation of the conserved glycine residue in the active-site P-loop
G129P
-
only low levels of protein production, NAT activity: 0.023 micromol/min/mg
G129P
-
only small amount of NAT protein, final protein yield: 0.75-0.5 mg of protein. Enzymatic activity: very low, not accurately measurable
G129S
-
final protein yield similar to wild-type: approximately 30 mg. Enzymatic activity: 4.152 micromol/min/mg, Km (mM): 0.447 (substrate: p-aminosalicylic acid)
G129S
-
mutation of the conserved glycine residue in the active-site P-loop
G129T
-
mutation of the conserved glycine residue in the active-site P-loop
G129T
-
only low levels of protein production, NAT activity: 4.758 micromol/min/mg
G129T
-
only small amount of NAT protein, final protein yield: 0.75-0.5 mg of protein. Enzymatic activity: 0.034 micromol/min/mg
G129V
-
mutation of the conserved glycine residue in the active-site P-loop
G129V
-
only low levels of protein production, NAT activity: 4.152 micromol/min/mg
G129V
-
only small amount of NAT protein, final protein yield: 0.75-0.5 mg of protein. Enzymatic activity: 0.022 micromol/min/mg
additional information
expression of BanatC in Escherichia coli affords higher-than-normal resistance to sulfonamide antibiotic sulfamethoxazole in the recombinant bacteria
additional information
Q81PT0
expression of BanatC in Escherichia coli affords higher-than-normal resistance to sulfonamide antibiotic sulfamethoxazole in the recombinant bacteria
additional information
Q81R98
expression of BanatC in Escherichia coli affords higher-than-normal resistance to sulfonamide antibiotic sulfamethoxazole in the recombinant bacteria
additional information
-
expression of BanatC in Escherichia coli affords higher-than-normal resistance to sulfonamide antibiotic sulfamethoxazole in the recombinant bacteria
additional information
native gene contains a c.580delG frameshift mutation leading to expression of a truncated protein. Artificial reintroduction of residue G580 in the NAT3 gene leads to a functional enzyme able to acetylate several arylamine drugs
additional information
-
native gene contains a c.580delG frameshift mutation leading to expression of a truncated protein. Artificial reintroduction of residue G580 in the NAT3 gene leads to a functional enzyme able to acetylate several arylamine drugs
additional information
-
construction of several insertion and deletion mutants of NAT2, overview
additional information
construction of several insertion and deletion mutants of NAT2, overview
additional information
construction of several insertion and deletion mutants of NAT2, overview
additional information
humans harboring certain genetic variations within the NAT genes exhibit increased likelihood of developing various cancer types, especially urinary bladder cancer, polymorphisms, the mutants exhibit reduced cellular activity, which is proposed to be due to their constitutive ubiquitylation and enhanced proteasomal degradation, overview
additional information
humans harboring certain genetic variations within the NAT genes exhibit increased likelihood of developing various cancer types, especially urinary bladder cancer, polymorphisms, the mutants exhibit reduced cellular activity, which is proposed to be due to their constitutive ubiquitylation and enhanced proteasomal degradation, overview
additional information
-
humans harboring certain genetic variations within the NAT genes exhibit increased likelihood of developing various cancer types, especially urinary bladder cancer, polymorphisms, the mutants exhibit reduced cellular activity, which is proposed to be due to their constitutive ubiquitylation and enhanced proteasomal degradation, overview
additional information
-
mutations responsible for reduced NAT1 stability and down-regulation occur in nature, the NAT1 slow acetylator phenotype is associated with a protection against spina bifida, a condition that is linked to the level of maternal folic acid intake
additional information
mutations responsible for reduced NAT1 stability and down-regulation occur in nature, the NAT1 slow acetylator phenotype is associated with a protection against spina bifida, a condition that is linked to the level of maternal folic acid intake
additional information
NAT2 random mutagenesis, developement of a system in which the activation of mutagens by recombinant human NAT 2, expressed in Escherichia coli, can be detected by the appearance of LacZ revertants, screening for variants of the human NAT2 sequence with altered activity, detailed overview
additional information
-
NAT2 random mutagenesis, developement of a system in which the activation of mutagens by recombinant human NAT 2, expressed in Escherichia coli, can be detected by the appearance of LacZ revertants, screening for variants of the human NAT2 sequence with altered activity, detailed overview
additional information
-
variable expression of isozyme NAT1 due to genetic polymorphism, gene regulation or environmental influences is associated with individual susceptibility to various cancers, overview
additional information
-
282T, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect silent, amino acid change none
additional information
-
345T, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect silent, amino acid change none
additional information
-
481T, single nucleotide polymorphism, point mutation in the arylamine N-acetyltransferase 2 gene, effect silent, amino acid change none
additional information
-
alleles NAT2*7 in patients indicate slow acetylators the ratio acetyl-INH/INH is 0.93-1.19 opposite 7.4 in patients with NAT2*4/NAT2*4 genotype, but in vitro similar kinetc parameters in NAT2*4 and NAT2*7 for INH are shown (Km (INH): 0.374 nM for NAT2*4 and 0.366 for NAT2*7)
additional information
-
ANDH, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
ANDH, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
ANDH, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
-
chimera production and site-directed mutagenesis identified amino acids 123, 125 and 127 that contribute significantly toward NAT1 and NAT2 substrate and kintic selectivity. Human NAT2 possesses a Ser residue at each of these three positions whereas NAT1 has Phe125, Arg127 and Tyr129
additional information
-
chimera production and site-directed mutagenesis identified amino acids 125, 127 and 129 that contribute significantly toward NAT1 and NAT2 substrate and kintic selectivity. Human NAT2 possesses a Ser residue at each of these three positions whereas NAT1 has Phe125, Arg127 and Tyr129
additional information
-
distribution of NAT1 genotypes is determined in 107 colon cancer cases, 77 rectal cancer cases, and 185 controls. In addition, possible occupational and nonoccupational risk factors are determined by a personal interview. Cancer cases and controls are derived from an area of former coal, iron, and steel industries, which is known for elevated colon cancer mortality. The result does not support a relevant impact of the NAT1 genotype on colorectal cancer risk development in the study area
additional information
-
genotoxic activation of PBTA derivatives using Salmonella typhimurium NM6001 (human NAT1-expressing strain), Salmonella typhimurium NM6002 (human NAT2-expressing strain), and Salmonella typhimurium NM6000 (O-acetyltransferase-deficient parent strain) in the presence of S9 mix is determined. PBTA-4 shows almost similar sensitivity in the NAT1-expressing strain and the NAT2-expressing strain, although NAT2-expressing strain exhibits relatively higher sensitivity to PBTA-6, PBTA-7, and PBTA-8 than NAT1-expressing strain. The NM6000 strain is not found to be sensitive to all of these chemicals The results support the view that O-acetylation by human NAT1 and NAT2 enzymes is involved in the genotoxic activation of PBTA compounds
additional information
-
genotypes of drug-metabolizing enzymes (NAT2, CYP2E15*B, CYP2E1*6, Glutathione-S-transferase (GST) M1 and GST T1) involved in isoniazid metabolism and the serum concentrations of isoniazid and its metabolites in 129 tuberculosis patients are investigated. Acetylating pathway of isoniazid to acetyl isoniazid tends to shift to the hydrolytic pathway generating hydrazine with the increase of mutant alleles in NAT2 gene
additional information
-
GG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
GG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
GG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
-
GGSG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
GGSG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
GGSG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
-
GRSG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
GRSG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
GRSG, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
-
HHEH, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
HHEH, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
HHEH, human NAT2 mutant, a 17-residue segment is deleted and replaced
additional information
-
human NAT1 and NAT2 are each 290 amino acids in length. They share 81% amino acid sequence identity, and only 28 of the 55 amino acid differences between the two proteins are non-conservative
additional information
-
NAT1*10, phenotype has higher than normal activity in some tissues, associated with increased risk of cancer
additional information
NAT1*10, phenotype has higher than normal activity in some tissues, associated with increased risk of cancer
additional information
-
NAT1*14, slow acetylator phenotype, loss of function alleles
additional information
NAT1*14, slow acetylator phenotype, loss of function alleles
additional information
-
NAT1*15, slow acetylator phenotype, loss of function alleles
additional information
NAT1*15, slow acetylator phenotype, loss of function alleles
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NAT1*17, slow acetylator phenotype, loss of function alleles
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NAT1*17, slow acetylator phenotype, loss of function alleles
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NAT1*19, slow acetylator phenotype, loss of function alleles
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NAT1*19, slow acetylator phenotype, loss of function alleles
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NAT1*22, slow acetylator phenotype, loss of function alleles
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NAT1*22, slow acetylator phenotype, loss of function alleles
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overexpression of human NAT1 in mice results in serious developmental problems: deevelopmentally deleterious effects are observed in which embryos either do not survive or show malformations with a phenotype in which the tail is kinked, reminiscent of a spina-bifida phenotype
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PHAG, human NAT2 mutant, a 17-residue segment is deleted and replaced
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PHAG, human NAT2 mutant, a 17-residue segment is deleted and replaced
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PHAG, human NAT2 mutant, a 17-residue segment is deleted and replaced
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QEGST, human NAT2 mutant, a 17-residue segment is deleted and replaced
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QEGST, human NAT2 mutant, a 17-residue segment is deleted and replaced
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QEGST, human NAT2 mutant, a 17-residue segment is deleted and replaced
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SDGSD, human NAT2 mutant, a 17-residue segment is deleted and replaced
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SDGSD, human NAT2 mutant, a 17-residue segment is deleted and replaced
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SDGSD, human NAT2 mutant, a 17-residue segment is deleted and replaced
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identification of seven non-synonymous single nucleotide variations in NAT1 gene, showing compromised enzyme function, mainly through destabilization of NAT1 protein and consequent activity loss
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identification of seven non-synonymous single nucleotide variations in NAT1 gene, showing compromised enzyme function, mainly through destabilization of NAT1 protein and consequent activity loss
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it is shown that a small amino acid (such as Gly or Ala) at position 429 (start of the active-site P-loop) is important not only for maintaining the functions of the active-site P-loop but also for maintaining the overall structural integrity of NAT enzymes. Results suggest that in addition to its role in substrate binding and selectivity, the active-site P-loop plays a wider structural role in NAT enzymes
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results show that amino acid 129, which is the start of the active-site P-loop, is important to be a small amino acid (such as Gly or Ala) not only for maintaining the functions of the active-site P-loop but also for maintaining the overall structural integrity of NAT enzymes. Results suggest that in addition to its role in substrate binding and selectivity, the active-site P-loop plays a wider structural role in NAT enzymes
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construction of NAT2 knockout mice, phenotype, overview
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construction of NAT2 knockout mice, phenotype, overview
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Nat1 knockout mice do not show an obvious phenotype, apart from the expected reduction in arylamine metabolism
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Nat2 knockout mice do not show an obvious phenotype, apart from the expected reduction in arylamine metabolism. From analyses following breeding studies it appears that lack of NAT2 affects the sex ratios in offspring such that there is an excess of females among heterozygotes
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Nat3 knockout mice: lack of Nat3 has no effect in the metabolism of arylamines by mice
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the developmental role of Nat2 is investigated using transgenic Nat2 knockout/lacZ knockin mice: The transgene is bred onto an A/J background and offspring are scored for developmental defects at weaning. After backcross generation eight, an ocular defect, ranging from cataract to microphthalmia and anophthalmia, is recorded among offspring of backcross and intercross pairs. While Nat2-/- mice are described as overtly aphenotypic, the presence of a Nat2 null allele in one or both parents can result in ocular defects. These ocular phenotypes and their association with Nat2 genotype indicate that the Nat2 locus may be responsible for the described microphthalmic phenotype
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replacement of the third domain of Mycobacterium marinum enzyme with that from Mycobacterium tuberculosis and vice versa
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replacement of the third domain of Mycobacterium marinum enzyme with that from Mycobacterium tuberculosis and vice versa
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deletion of the nat gene causes an extended lag phase in strain BCG and a cell morphology associated with an altered pattern of cell wall mycolates, overview
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deletion of the NAT gene results in an increased sensitivity to isoniazid by up to 3fold. Furthermore, growth of NAT deleted strains is delayed, organisms become more susceptible to antibiotics such as gentamycin and the characteristic mycobacterial cell wall lipid components are not present. NAT gene is essential for survival of Mycobacterium bovis within macrophage
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effect of deleting NAT gene: slows growth, increases sensitivity to isoniazid, changes colony morphology, reduces the thickness of the cell wall of individual cells, decreases mycolic acid and complex lipids but not phosholipids, leads to intracellular killing of Mycobacterium bovis in macrophages
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deletion of the NAT gene results in an increased sensitivity to isoniazid by up to 3fold. Furthermore, growth of NAT deleted strains is delayed, organisms become more susceptible to antibiotics such as gentamycin and the characteristic mycobacterial cell wall lipid components are not present
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deletion of the NAT gene results in an increased sensitivity to isoniazid by up to 3fold. Furthermore, growth of NAT deleted strains is delayed, organisms become more susceptible to antibiotics such as gentamycin and the characteristic mycobacterial cell wall lipid components are not present
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overexpression in Mycobacterium bovis results in a decreased susceptibility to isoniazid in the slow growing mycobacterium
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overexpression in Mycobacterium bovis results in a decreased susceptibility to isoniazid in the slow growing mycobacterium
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construction of a chromosomal knockout mutant of wbpD is incapable of producing either long-chain B-band O antigen, with 2 or more repeating units, or semi-rough LPS, i.e. lipid A-core + one repeat, adding wbpD in trans restores LPS production to the wild-type level, overview
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truncation mutants with either C-terminal undecapeptide or C-terminal 85 amino acids missing, in contrast to complete protein, mutants hydrolyse acetyl-CoA even in the absence of arylamine substrate
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construction of a natA disruption mutant that is catalytically inactive
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construction of a natA disruption mutant that is catalytically inactive
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construction of a natA disruption mutant that is catalytically inactive
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