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Literature summary extracted from

  • Grant, D.M.
    Structures of human arylamine N-acetyltransferases (2008), Curr. Drug Metab., 9, 465-470.
    View publication on PubMed

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.5 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 Homo sapiens
2.3.1.5 F125S mutant produces a 220fold increased affinity for the NAT2-selective substrate sulfamethazine, Km (sulfamethazine): 0.02 mM Homo sapiens
2.3.1.5 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 Homo sapiens
2.3.1.5 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 Homo sapiens
2.3.1.5 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 Homo sapiens
2.3.1.5 R127S mutant shows a 42fold decreased affinity for the NAT1-selective substrate p-aminobenzoic acid Homo sapiens
2.3.1.5 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 Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.1.5 additional information
-
additional information NAT1 shows much higher affinity for p-amino benzoic acid than for sulfamethazine while NAT2 shows the opposite selectivity Homo sapiens
2.3.1.5 0.01
-
p-Aminobenzoic acid at fixed concentration of 0.1 mM acetyl-CoA Homo sapiens
2.3.1.5 0.02
-
sulfamethazine mutant F125S Homo sapiens
2.3.1.5 0.12
-
sulfamethazine at fixed concentration of 0.1 mM acetyl-CoA Homo sapiens
2.3.1.5 1.2
-
sulfamethazine at fixed concentration of 0.1 mM acetyl-CoA Homo sapiens
2.3.1.5 2.9
-
p-Aminobenzoic acid at fixed concentration of 0.1 mM acetyl-CoA Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.5 Homo sapiens
-
-
-
2.3.1.5 Mesocricetus auratus
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
2.3.1.5 acetyl-CoA + an arylamine = CoA + an N-acetylarylamine it is shown that the formation of a thiolate-imidazolium ion pair by Cys68 and His107 is involved in the catylytic mechanism. Asp122 is required for optimal catalysis and structural stability. Enzyme deacetylation step proceeds via nucleophilic attack for acceptor amines with pKa values less than 5.5 and by deprotonation of a tetrahedral intermediate for amines with pKa values greater than 5.5 Mesocricetus auratus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.5 acetyl-CoA + p-aminobenzoic acid
-
Homo sapiens CoA + N-acetyl-4-aminobenzoic acid
-
?
2.3.1.5 acetyl-CoA + sulfamethazine
-
Homo sapiens CoA + N-acetyl-sulfamethazine
-
?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.5 arylamine N-acetyltransferase 1
-
Homo sapiens
2.3.1.5 arylamine N-acetyltransferase 2
-
Homo sapiens
2.3.1.5 arylamine N-acetyltransferase 2
-
Mesocricetus auratus
2.3.1.5 NAT1
-
Homo sapiens
2.3.1.5 NAT2
-
Homo sapiens
2.3.1.5 NAT2
-
Mesocricetus auratus

Cofactor

EC Number Cofactor Comment Organism Structure
2.3.1.5 acetyl-CoA
-
Homo sapiens
2.3.1.5 acetyl-CoA
-
Mesocricetus auratus