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Table 1 Arylamine activity profiles of native and engineered NATs in relation to substrate physicochemical properties

From: Differences between murine arylamine N-acetyltransferase type 1 and human arylamine N-acetyltransferase type 2 defined by substrate specificity and inhibitor binding

 

NAT enzymes: % specific activity values

 

(HUMAN) NAT1*4

(MOUSE) NAT2*1

(MESAU) NAT2*1

(MOUSE) NAT2 F125S

(MOUSE) NAT2 R127G

(MOUSE) NAT2 R127L

(MOUSE) NAT1*1

(HUMAN) NAT2*4

NAT substrates

F125

-

-

S

-

-

Y

S

R127

-

-

-

G

L

G

S

Y129

-

L

-

-

-

-

S

Negatively charged arylamines at pH 8.0

Folate catabolites

4AB glu

20 ± 1

87 ± 1

57 ± 3

19 ± 1

9 ± 1

8 ± 1

8 ± 7

3 ± 1

4ABA

100 ± 2

100 ± 2

100 ± 6

70 ± 2

8 ± 1

8 ± 1

48 ± 6

6 ± 1

Salicylic acids

4AS

67 ± 2

55 ± 1

74 ± 3

75 ± 3

27 ± 1

13 ± 1

88 ± 6

7 ± 1

5AS

64 ± 3

37 ± 1

30 ± 1

74 ± 1

94 ± 1

65 ± 9

76 ± 6

64 ± 2

Neutral electron-rich arylamines at pH 8.0

Halogenated anilines

4CA

36 ± 2

46 ± 4

61 ± 2

56 ± 2

54 ± 3

70 ± 1

18 ± 3

71 ± 3

4BA

50 ± 1

52 ± 2

72 ± 1

47 ± 2

70 ± 1

81 ± 11

28 ± 6

72 ± 1

4IA

63 ± 1

72 ± 3

81 ± 1

69 ± 2

97 ± 1

74 ± 8

28 ± 3

65 ± 2

Alkyl- and aryl-oxyanilines

ANS

56 ± 2

88 ± 6

89 ± 1

100 ± 3

97 ± 4

77 ± 10

48 ± 1

9 ± 2

4AV

25 ± 2

90 ± 1

32 ± 1

90 ± 1

66 ± 3

100 ± 10

28 ± 6

57 ± 3

HOA

12 ± 4

23 ± 2

35 ± 1

47 ± 1

59 ± 3

80 ± 8

3 ± 4

51 ± 2

POA

17 ± 7

20 ± 2

22 ± 1

62 ± 2

67 ± 1

61 ± 2

6 ± 1

62 ± 11

Other aniline

SMZ

1 ± 1

4 ± 1

1 ± 1

1 ± 1

19 ± 2

3 ± 1

88 ± 6

46 ± 1

Arylhydrazines

INH

0 ± 2

2 ± 2

1 ± 1

38 ± 2

63 ± 10

76 ± 14

100 ± 6

62 ± 2

HDZ

2 ± 1

8 ± 2

3 ± 1

19 ± 1

100 ± 2

95 ± 1

68 ± 6

100 ± 1

  1. Percentage specific activity values of native and engineered mammalian NAT proteins are shown. A value of 100% is attributed to the substrate towards which the isoform in question has the highest specific activity. All results shown are the mean of 3 measurements ± standard deviation. Percentages ≥90% for each isoenzyme were compared by ANOVA using a Student’s t-test and statistically similar values are emboldened. Isoforms are ordered according to increasing number of residue differences within the active site in relation to (HUMAN)NAT1*4. Residues identical to those in (HUMAN)NAT1*4 are labelled with a hyphen; residues different from the corresponding residue of (HUMAN)NAT1*4 are specified. Substrates are ordered according to the number of negative charges at pH 8.0, then to electron-richness and increasing size of aromatic substituents. The chemical structures and physicochemical properties of the chemicals used as substrates for NAT in this study are shown in Additional file 3: Table S1.