Crystal structure of human thioredoxin revealing an unraveled helix and exposed S-nitrosation site.
Crystal structure of human thioredoxin revealing an unraveled helix and exposed S-nitrosation site.
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人硫氧还蛋白的晶体结构揭示了未解开的螺旋和暴露的 S-亚硝化位点。
DOI：
10.1002/pro.455
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Montfort,WilliamR
中科院分区：
文献类型：
--
作者：
Weichsel,Andrzej;Kem,Michelle;Montfort,WilliamR
硫氧还蛋白使用 CXXC 基序减少所有细胞中的二硫键和其他硫醇修饰。人硫氧还蛋白 1 的不同寻常之处在于，它在 105 个氨基酸序列中额外编码了 3 个半胱氨酸，每个半胱氨酸都与其他还原活性有关。 Cys 62 和 Cys 69 埋藏在蛋白质内部，位于短螺旋（螺旋 3）的两端，但在氧化条件下可以形成二硫键。 Cys 62 很容易被 S-亚硝化，产生 SNO 修饰，该修饰也被隐藏。在这里，我们展示了 C69S/C73S 突变蛋白在氧化 (1.5 Å) 和还原 (1.1 Å) 条件下的两种晶体结构。在氧化结构中，螺旋 3 被解开并显示出新的构象，该构象通过一系列新的氢键和与相邻分子中的 Cys 62 的二硫键来稳定。新构象解释了完全埋藏的残基如何参与 SNO 交换反应。
Thioredoxins reduce disulfide bonds and other thiol modifications in all cells using a CXXC motif. Human thioredoxin 1 is unusual in that it codes for an additional three cysteines in its 105 amino acid sequence, each of which have been implicated in other reductive activities. Cys 62 and Cys 69 are buried in the protein interior and lie at either end of a short helix (helix 3), and yet can disulfide link under oxidizing conditions. Cys 62 is readilyS‐nitrosated, giving rise to a SNO modification, which is also buried. Here, we present two crystal structures of the C69S/C73S mutant protein under oxidizing (1.5 Å) and reducing (1.1 Å) conditions. In the oxidized structure, helix 3 is unraveled and displays a new conformation that is stabilized by a series of new hydrogen bonds and a disulfide link with Cys 62 in a neighboring molecule. The new conformation provides an explanation for how a completely buried residue can participate in SNO exchange reactions.