Molecular characterization of ST1C1-related human sulfotransferase.
Carcinogenic arylamines such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) are metabolically activated by mammalian sulfotransferases to form N-hydroxyarylamine O-sulfates. We previously showed that rat ST1C1 efficiently mediate these activations. These reactions occur in liver cytosols of humans as well as rats. However, the enzyme responsible for N-OH-AAF activation has not been identified in humans. In the present study, a human cDNA (ST1C2) encoding a sulfotransferase showing a high similarity with ST1C1, has been isolated from a human fetal liver cDNA library and expressed using a bacterial expression system. A clear difference was observed in the pH optima for p-nitrophenol sulfation between ST1C2 and ST1C1 expressed in Escherichia coli. In addition, ST1C2 did not mediate 3'-phosphoadenosine-5'-phosphosulfate-dependent DNA binding of N-OH-AAF. These results suggest that human ST1C2 has a clear different substrate specificity, in spite of the structural similarity, with rat ST1C1.
Yoshinari
K
K
Division of Drug Metabolism and Molecular Toxicology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Nagata
K
K
Shimada
M
M
Yamazoe
Y
Y
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006881:Hydroxyacetylaminofluorene / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism
D002273:Carcinogens; D006881:Hydroxyacetylaminofluorene; C513319:SULT1C2 protein, human; D015238:Sulfotransferases