Borchardt R T, Wu Y S
J Med Chem. 1976 Sep;19(9):1099-1103. doi: 10.1021/jm00231a004.
The configuration at the asymmetric sulfonium pole of S-adenosyl-L-methionine (SAM) necessary for optimal enzymatic binding and methyl donation has been elucidated in this study. For the transmethylations catalyzed by catechol O-methyltransferase, phenylethanolamine N-methyltransferase, histamine N-methyltransferase, and hydroxyindole O-methyltransferase, it was demonstrated that only the natural (-) enantiomer of SAM was active as a methyl donor. The corresponding (+)-SAM, which was prepared by enzymatic resolution of synthetic (+/-)-SAM, was shown to be inactive as a methyl donor in these enzymatic reactions. The (+)-SAM was found, however, to be a potent inhibitor of each of these enzyme-catalyzed transmethylations. These results suggest that the (+) enantiomer offers a nonproductive configuration for the methyl-transfer reaction itself; however, this configuration fails to hamper enzymatic binding. These results are discussed relative to the geometric requirements necessary for the methyl-transfer reaction and the requirements for enzymatic binding.
本研究阐明了S-腺苷-L-甲硫氨酸（SAM）的不对称锍极处的构型，这一构型对于最佳酶结合和甲基供体作用是必需的。对于由儿茶酚O-甲基转移酶、苯乙醇胺N-甲基转移酶、组胺N-甲基转移酶和羟基吲哚O-甲基转移酶催化的转甲基反应，结果表明只有天然的（-）对映体的SAM作为甲基供体具有活性。通过合成（+/-）-SAM的酶法拆分制备的相应（+）-SAM在这些酶促反应中作为甲基供体无活性。然而，发现（+）-SAM是这些酶催化的转甲基反应中每一种的有效抑制剂。这些结果表明，（+）对映体为甲基转移反应本身提供了一种无效构型；然而，这种构型并不妨碍酶结合。相对于甲基转移反应所需的几何要求和酶结合要求，对这些结果进行了讨论。
