Gadjeva M, Dodds A W, Taniguchi-Sidle A, Willis A C, Isenman D E, Law S K
The Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, United Kingdom.
J Immunol. 1998 Jul 15;161(2):985-90.
The covalent binding of C3 to target molecules on the surfaces of pathogens is crucial in most complement-mediated activities. When C3 is activated, the acyl group is transferred from the sulfhydryl of the internal thioester to the hydroxyl group of the acceptor molecule; consequently, C3 is bound to the acceptor surface by an ester bond. It has been determined that the binding reaction of the B isotype of human C4 uses a two-step mechanism. Upon activation, a His residue first attacks the internal thioester to form an acyl-imidazole bond. The freed thiolate anion of the Cys residue of the thioester then acts as a base to catalyze the transfer of the acyl group from the imidazole to the hydroxyl group of the acceptor molecule. In this article, we present results which indicate that this two-step reaction mechanism also occurs in C3.
在大多数补体介导的活性中，C3与病原体表面靶分子的共价结合至关重要。当C3被激活时，酰基从内部硫酯的巯基转移到受体分子的羟基上；因此，C3通过酯键与受体表面结合。已确定人C4的B同种型的结合反应采用两步机制。激活后，一个组氨酸残基首先攻击内部硫酯形成酰基咪唑键。硫酯的半胱氨酸残基释放出的硫醇盐阴离子然后作为碱催化酰基从咪唑转移到受体分子的羟基上。在本文中，我们展示的结果表明这种两步反应机制也存在于C3中。
