Irreversible inhibition of glutamate decarboxylase by alpha-(fluoromethyl)glutamic acid.
Irreversible inhibition of glutamate decarboxylase by alpha-(fluoromethyl)glutamic acid.
复制标题
α-（氟甲基）谷氨酸对谷氨酸脱羧酶的不可逆抑制。
DOI：
10.1021/bi00506a010
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发表时间：
1981
期刊：
影响因子：
2.9
通讯作者：
R. Rando
中科院分区：
文献类型：
--
作者：
D. Kuo;R. Rando
合成了α-（氟甲基）谷氨酸（FMG），并显示其是来自大肠杆菌的谷氨酸脱羧酶（EC 4.1.1.15）的活性位点定向的不可逆抑制剂。活性对映体的KI为1.4 μ M，kinh = 5.9 × 10（-3）s-1。底物的酶，如L-谷氨酸，和竞争性抑制剂，如柠檬酸，降低FMG介导的失活的酶的速率。酶的紫外光谱的深刻变化伴随着失活过程。当使用[3 H]-FMG时，可以表明该酶以与失活相同的速率掺入放射性。存在1：1化学计量的[3 H]FMG掺入酶的磷酸吡哆醛结合亚基。从这些和其他研究得出结论，FMG是酶的底物和烷基化它作为这种营业额的结果。
alpha-(Fluoromethyl)glutamic acid (FMG) was synthesized and shown to be an active site directed irreversible inhibitor of glutamate decarboxylase (EC 4.1.1.15) from Escherichia coli. The KI for the active enantiomer is 1.4 microM, and the kinh = 5.9 X 10(-3) s-1. Substrates for the enzyme, such as L-glutamate, and competitive inhibitors, such as citrate, decrease the rates of FMG-mediated inactivation of the enzyme. A profound change in the ultraviolet spectrum of the enzyme accompanies the inactivation process. When [3H]-FMG is used, it can be shown that the enzyme incorporates radioactivity at the same rate as that of inactivation. There is a 1:1 stoichiometry of [3H]FMG incorporated to pyridoxal phosphate binding subunits of the enzyme. From these and other studies it is concluded that FMG is a substrate for the enzyme and alkylates it as a consequence of this turnover.