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Literature summary extracted from

  • Ragunathan, N.; Dairou, J.; Pluvinage, B.; Martins, M.; Petit, E.; Janel, N.; Dupret, J.M.; Rodrigues-Lima, F.
    Identification of the xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 as a new target of cisplatin in breast cancer cells: molecular and cellular mechanisms of inhibition (2008), Mol. Pharmacol., 73, 1761-1768.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.3.1.5 medicine the results suggest that the irreversible inactivation of NAT1 by cysplatin may at least partly contribute to the pharmacological and, or toxicological effects of cisplatin Homo sapiens
2.3.1.5 molecular biology results show that cisplatin inactivates the NAT1 enzyme by forming an adduct with the catalytic cysteine residue of the enzyme Mus musculus
2.3.1.5 molecular biology results show that cisplatin inactivates the NAT1 enzyme by forming an adduct with the catalytic cysteine residue of the enzyme Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.5 expressed as a His-tagged fusion protein in Escherichia coli Homo sapiens
2.3.1.5 into the pET28a vector for expression in Escherichia coli BL21DE3 cells Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.5 cisplatin exposure of MCF-7 breast cancer cells to cisplatin at clinically relevant concentrations (below 0.4 nM) causes significant dose-dependent inhibition of the endogenous NAT1 enzyme. The incubation of NAT1 with various concentrations of cisplatin results in the dose-dependent modification of cysteine residues, as indicated by the disappearance of fluorescein-conjugated iodoacetamide labeling Homo sapiens
2.3.1.5 cisplatin treating C57BL/6J mice with cisplatin significantly decreases murine Nat2 (murine counterpart of human NAT1) enzymatic function in the liver (25% inhibition), kidney (40% inhibition), and blood cells (50% inhibition) Mus musculus

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.5 Homo sapiens
-
-
-
2.3.1.5 Mus musculus
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.1.5
-
 Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.1.5 blood
-
 Mus musculus
-
2.3.1.5 kidney
-
 Mus musculus
-
2.3.1.5 liver
-
 Mus musculus
-
2.3.1.5 MCF-7 cell
-
 Homo sapiens
-
2.3.1.5 MDA-MB-231 cell
-
 Homo sapiens
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
2.3.1.5 additional information
-
 wild-type enzyme 100% activity, + cisplatin 9%, + AcCoA and cisplatin 13 - 77%, depending on the AcCoA concentration, + CoA and cysplatin 7% Homo sapiens

Substrates and Products (Substrate)

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

Synonyms

EC Number Synonyms Comment Organism
2.3.1.5 arylamine N-acetyltransferase 1
-
 Mus musculus
2.3.1.5 arylamine N-acetyltransferase 1
-
 Homo sapiens
2.3.1.5 NAT1
-
 Mus musculus
2.3.1.5 NAT1
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.1.5 37
-
 assay at Mus musculus
2.3.1.5 37
-
 assay at Homo sapiens
2.3.1.5 37
-
 activity assay Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.5 7.5
-
 assay at Mus musculus
2.3.1.5 7.5
-
 assay at Homo sapiens
2.3.1.5 7.5
-
 activity assay Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.3.1.5 additional information
-
 additional information the second-order rate constant (kinact) for the inactivation of NAT1 by cisplatin is estimated at 700/M min Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.3.1.5 0.1
-
 in MCF-7 breast cancer cells Homo sapiens cisplatin
2.3.1.5 0.1
-
 in MCF7-cells, similar results with MDA-MB-231 cells Homo sapiens cisplatin