Structural basis of the binding specificity of the thioester-containing proteins, C4, C3 and alpha-2-macroglobulin.
Structural basis of the binding specificity of the thioester-containing proteins, C4, C3 and alpha-2-macroglobulin.
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DOI：
10.1159/000463039
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
D. Aw;Lawal Sk
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文献类型：
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作者：
D. Aw;Lawal Sk
我们以前已经注意到人C4-A和C4-B的共价结合反应的特异性有很大的差异。在这里，我们报告了其他三种含有硫酯的蛋白质的数据。人C3与甘氨酸无反应，但与甘油的反应性(k‘/Ko=23.0M-1)与人C4-B(k’/Ko=15.5M-1)相似。人α2-巨球蛋白与甘氨酸(k‘/ko=206M-1)的反应类似于C4-B(k’/ko=119M-1)，但与甘油(k‘/ko=1.2M-1)的反应类似于C4-A(k’/ko=1.3M-1)。小鼠C4与甘氨酸(k‘/Ko=136M-1)和甘油(k’/Ko=26.0M-1)的反应均类似于C4-B。在这些蛋白质中，只有C4-A与甘氨酸有很高的反应速度(k‘/ko=13,400M-1)。通过对这些蛋白质一级结构的比较，我们提出了人类前C4分子1105和1106位的Leu Asp：Ile His取代，作为主要负责这些蛋白质结合特异性的残基。Leu：Ile的变化不会显著影响这些蛋白质的反应性，但由于变构原因可能是必要的。C4-A中的Asp和C4-B中的His似乎是主要的特异性定义残基。
We have previously noted a large difference in the specificity of the covalent binding reaction of human C4-A and C4-B. Here we report data on three other thioester-containing proteins. Human C3 is unreactive with glycine but its reactivity with glycerol (k'/ko = 23.0 M-1) is similar to that of human C4-B (k'/ko = 15.5 M-1). Human alpha 2-macroglobulin reacts with glycine (k'/ko = 206 M-1) in a manner similar to C4-B (k'/ko = 119 M-1) but its reactivity with glycerol (k'/ko = 1.2 M-1) is C4-A like (k'/ko = 1.3 M-1). Mouse C4 is C4-B like in its reaction with both glycine (k'/ko = 136 M-1) and glycerol (k'/ko = 26.0 M-1). Of these proteins, only C4-A shows a very high rate of reaction with glycine (k'/ko = 13,400 M-1). The comparison of the primary structures of these proteins has allowed us to propose the Leu Asp:Ile His substitutions at positions 1105 and 1106 in the human pro-C4 molecule as the residues largely responsible for the binding specificities of these proteins. The Leu:Ile change would not markedly affect the reactivity of these proteins, but may be necessary for allosteric reasons. The Asp in C4-A and His in C4-B seem likely to be the major specificity-defining residues.