Yoshinari K, Nagata K, Ogino M, Fujita K, Shiraga T, Iwasaki K, Hata T, Yamazoe Y
Division of Drug Metabolism and Molecular Toxicology, Faculty of Pharmaceutical Sciences, Tohoku University, Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan.
J Biochem. 1998 Mar;123(3):479-86. doi: 10.1093/oxfordjournals.jbchem.a021961.
A cDNA of amine sulfotransferase-RB1 (AST-RB1), which efficiently catalyzes 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP) sulfation, has been isolated by immunoscreening of a rabbit liver cDNA library. The cDNA consisted of 1,117 base pairs and encoded a protein of 301 amino acids with a molecular weight of 35,876. The deduced amino acid sequence matched at six positions those of peptide fragments obtained from purified AST-RB1 protein. The sequence had less than 38% identity at the amino acid level with cytosolic sulfotransferases in mammals, although high degrees of similarity were observed with regions conserved throughout mammalian sulfotransferases. These results indicate that AST-RB1, arbitrarily named sulfotransferase 3A1 (ST3A1), constitutes a new and third gene family of cytosolic sulfotransferases in mammals. ST3A1 expressed in Escherichia coli as a fused protein catalyzed sulfation of amines such as PTHP, aniline, 4-chloroaniline, 2-naphthylamine, and desipramine, but barely O-sulfation of typical aryl and hydroxysteroid sulfotransferase substrates. These data unequivocally demonstrate the existence of a cytosolic sulfotransferase showing a high selectivity for amine substrates, and indicate that multiple forms of sulfotransferase mediate sulfation of xenobiotics in mammalian livers.
通过对兔肝cDNA文库进行免疫筛选，分离出了一种能高效催化4-苯基-1,2,3,6-四氢吡啶（PTHP）硫酸化的胺基硫酸转移酶-RB1（AST-RB1）的cDNA。该cDNA由1117个碱基对组成，编码一个301个氨基酸的蛋白质，分子量为35876。推导的氨基酸序列在六个位置与从纯化的AST-RB1蛋白获得的肽片段的序列相匹配。尽管在整个哺乳动物硫酸转移酶中观察到高度相似的保守区域，但该序列在氨基酸水平上与哺乳动物胞质硫酸转移酶的同一性低于38%。这些结果表明，AST-RB1（任意命名为硫酸转移酶3A1，即ST3A1）构成了哺乳动物胞质硫酸转移酶的一个新的第三基因家族。在大肠杆菌中作为融合蛋白表达的ST3A1催化了诸如PTHP、苯胺、4-氯苯胺、2-萘胺和地昔帕明等胺类的硫酸化，但对典型的芳基和羟基类固醇硫酸转移酶底物几乎没有O-硫酸化作用。这些数据明确证明了存在一种对胺底物具有高选择性的胞质硫酸转移酶，并表明多种形式的硫酸转移酶介导了哺乳动物肝脏中外源化合物的硫酸化。
