Stereochemical course of the transmethylation catalyzed by catechol O-methyltransferase.
Stereochemical course of the transmethylation catalyzed by catechol O-methyltransferase.
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DOI：
10.1016/s0021-9258(19)70536-5
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发表时间：
1980-10
期刊：
影响因子：
--
通讯作者：
R. Woodard;M. Tsai;H. Floss;P. Crooks;J. Coward
中科院分区：
文献类型：
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作者：
R. Woodard;M. Tsai;H. Floss;P. Crooks;J. Coward
研究了邻苯二酚O-甲基转移酶催化甲基转移的立体过程。以S-腺苷蛋氨酸(ADO-Met)为载体，通过不对称的~1H、~2H和~3H标记，得到了手性甲基。从大鼠肝脏中提纯的儿茶酚O-甲基转移酶与该底物的两个非对映异构体以肾上腺素或原儿茶酸为受体孵育，得到相应的甲基化儿茶酚。这些都被降解，以在一系列立体化学反应中将甲氧基转化为乙酸甲酯，然后对其构型进行分析。结果表明，甲基从ADOMet到任一受体的转移是以反转方式进行的。因此，邻苯二酚O-甲基转移酶反应涉及在SN2过程中将甲基从ADOMet的硫直接转移到邻苯二酚的氧，而不需要甲基化的酶中间体。
The steric course of the methyl group transfer catalyzed by catechol O-methyltransferase was studied using S-adenosylmethionine (AdoMet) carrying a methyl group made chiral by labeling with 1H, 2H, and 3H in an asymmetrical arrangement. Incubation of the two diastereomers of this substrate with catechol O-methyl-transferase purified from rat liver and epinephrine or protocatechuic acid as acceptor gave the corresponding methylated catechols. These were degraded to convert the methoxy group in a series of stereochemically unambiguous reactions into the methyl group of acetate, which was then analyzed for its configuration. The results indicate that the transfer of the methyl group from AdoMet to either acceptor occurs in an inversion mode. The catechol O-methyltransferase reaction thus involves a direct transfer of the methyl group from the sulfur of AdoMet to the oxygen of the catechol in an SN2 process, without a methylated enzyme intermediate.