The reaction mechanism of the internal thioester in the human complement component C4
The reaction mechanism of the internal thioester in the human complement component C4
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DOI：
10.1038/379177a0
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发表时间：
1996-01-11
期刊：
影响因子：
64.8
通讯作者：
Law, SKA
中科院分区：
文献类型：
--
作者：
Dodds, AW;Ren, XD;Law, SKA
从体内消除病原体的关键步骤是补体蛋白 C3 和 C4 与其表面的共价结合 (1-5)。这些蛋白质的蛋白水解激活导致构象变化(6,7)，并且暴露内部硫酯(8-10)，其与目标表面上的氨基或羟基反应形成酰胺或酯键，或者被水解(11-15)。我们在这里报告，人类 C4A 同型的结合涉及氨基亲核试剂和硫酯之间的直接反应。 C4B 同种型使用两步机制。 1,106 位的组氨酸（C4A 中的天冬氨酸）首先攻击硫酯，形成酰基咪唑中间体。然后释放的硫醇充当碱，催化酰基转移到氨基和羟基亲核试剂（包括水）。
A KEY step in the elimination of pathogens from the body is the covalent binding of complement proteins C3 and C4 to their surfaces(1-5). Proteolytic activation of these proteins results in a conformational change(6,7), and an internal thioester(8-10) is exposed which reacts with amino or hydroxyl groups on the target surface to form amide or ester bonds, or is hydrolysed(11-15). We report here that the binding of the human C4A isotype involves a direct reaction between amino-nucleophiles and the thioester. A two-step mechanism is used by the C4B isotype. The histidine at position 1,106 (aspartic acid in C4A) first attacks the thioester to form an acyl-imidazole intermediate. The released thiol then acts as a base to catalyse the transfer of the acyl group to amino- and hydroxyl-nucleophiles, including water.