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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.