Dodds A W, Ren X D, Willis A C, Law S K
Department of Biochemistry, University of Oxford, UK.
Nature. 1996 Jan 11;379(6561):177-9. doi: 10.1038/379177a0.
A key step in the elimination of pathogens from the body is the covalent binding of complement proteins C3 and C4 to their surfaces. Proteolytic activation of these proteins results in a conformational change, and an internal thioester is exposed which reacts with amino or hydroxyl groups on the target surface to form amide or ester bonds, or is hydrolysed. 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.
从体内清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。这些蛋白质的蛋白水解激活导致构象变化，暴露内部硫酯，其与靶表面上的氨基或羟基反应形成酰胺或酯键，或被水解。我们在此报告，人类C4A同种型的结合涉及亲核氨基与硫酯之间的直接反应。C4B同种型采用两步机制。第1106位的组氨酸（C4A中的天冬氨酸）首先攻击硫酯以形成酰基咪唑中间体。释放的硫醇然后作为碱催化酰基转移至亲核氨基和羟基，包括水。
