A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol
A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol
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DOI：
10.1074/jbc.m110246200
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发表时间：
2002-03-29
影响因子：
4.8
通讯作者：
Thomas, DJ
中科院分区：
文献类型：
--
作者：
Lin, S;Shi, Q;Thomas, DJ
S-腺苷-L-甲硫氨酸（蛋氨酸）：砷（III）甲基转移酶，从成年雄性Fischer 344大鼠的肝胞液中纯化，催化蛋氨酸的甲基转移至三价砷，产生甲基化和二甲基化砷。在含有酶、蛋氨酸、二硫苏糖醇、谷胱甘肽（GSH）和亚砷酸盐的反应混合物中，甲基化砷的生产动力学与亚砷酸盐产生的单甲基化砷是产生二甲基化砷的第二甲基化反应的底物的方案一致。该蛋白质的mRNA预测了一个369个氨基酸残基的蛋白质（分子量41056），其中包含常见的甲基转移酶序列基序。它的序列与Cyt 19相似，Cyt 19是一种推定的甲基转移酶，在人类和小鼠组织中表达。逆转录-聚合酶链反应检测大鼠组织和HepG 2细胞（一种使亚砷酸和甲基亚胂酸甲基化的人类细胞系）中的S-腺苷-L-甲硫氨酸：砷（III）甲基转移酶mRNA。在UROtsa细胞中未检测到S-腺苷-L-甲硫氨酸：砷（III）甲基转移酶mRNA，UROtsa细胞是一种不使亚砷酸盐甲基化的永生化人尿路上皮细胞系。由于砷的甲基化是其代谢的一个重要特征，这种酶的表征将提高我们对这种类金属的代谢及其作为毒素和致癌物的作用的理解。
S-Adenosyl-L-methionine (AdoMet):arsenic (III) methyltransferase, purified from liver cytosol of adult male Fischer 344 rats, catalyzes transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals. The kinetics of production of methylated arsenicals in reaction mixtures containing enzyme, AdoMet, dithiothreitol, glutathione (GSH), and arsenite are consistent with a scheme in which monomethylated arsenical produced from arsenite is the substrate for a second methylation reaction that yields dimethylated arsenical. The mRNA for this protein predicts a 369-amino acid residue protein (molecular mass 41056) that contains common methyltransferase sequence motifs. Its sequence is similar to Cyt19, a putative methyltransferase, expressed in human and mouse tissues. Reverse transcription-polymerase chain reaction detects S-adenosyl-L-methionine:arsenic(III) methyltransferase m-RNA in rat tissues and in HepG2 cells, a human cell line that methylates arsenite and methylarsonous acid. S-Adenosyl-L-methionine:arsenic(III) methyltransferase mRNA is not detected in UROtsa cells, an immortalized human urothelial cell line that does not methylate arsenite. Because methylation of arsenic is a critical feature of its metabolism, characterization of this enzyme will improve our understanding of this metalloid's metabolism and its actions as a toxin and a carcinogen.