Eklund H, Gleason F K, Holmgren A
Department of Molecular Biology, Swedish University of Agricultural Sciences, Uppsala.
Proteins. 1991;11(1):13-28. doi: 10.1002/prot.340110103.
Three-dimensional models have been constructed of homologous thioredoxins and protein disulfide isomerases based on the high resolution x-ray crystallographic structure of the oxidized form of Escherichia coli thioredoxin. The thioredoxins, from archebacteria to humans, have 27-69% sequence identity to E. coli thioredoxin. The models indicate that all the proteins have similar three-dimensional structures despite the large variation in amino acid sequences. As expected, residues in the active site region of thioredoxins are highly conserved. These include Asp-26, Ala-29, Trp-31, Cys-32, Gly-33, Pro-34, Cys-35, Asp-61, Pro-76, and Gly-92. Similar residues occur in most protein disulfide isomerase sequences. Most of these residues form the surface around the active site that appears to facilitate interactions with other enzymes. Other structurally important residues are also conserved. A proline at position 40 causes a kink in the alpha-2 helix and thus provides the proper position of the active site residues at the amino end of this helix. Pro-76 is important in maintaining the native structure of the molecule. In addition, residues forming the internal contact surfaces between the secondary structural elements are generally unchanged such as Phe-12, Val-25, and Phe-27.
基于大肠杆菌硫氧还蛋白氧化形式的高分辨率X射线晶体结构，构建了同源硫氧还蛋白和蛋白质二硫键异构酶的三维模型。从古细菌到人类的硫氧还蛋白与大肠杆菌硫氧还蛋白的序列同一性为27%-69%。这些模型表明，尽管氨基酸序列差异很大，但所有蛋白质都具有相似的三维结构。正如预期的那样，硫氧还蛋白活性位点区域的残基高度保守。这些残基包括Asp-26、Ala-29、Trp-31、Cys-32、Gly-33、Pro-34、Cys-35、Asp-61、Pro-76和Gly-92。大多数蛋白质二硫键异构酶序列中也存在类似的残基。这些残基中的大多数形成活性位点周围的表面，似乎有助于与其他酶相互作用。其他结构上重要的残基也保守。40位的脯氨酸导致α-2螺旋出现扭结，从而在该螺旋的氨基末端提供活性位点残基的正确位置。Pro-76对于维持分子的天然结构很重要。此外，形成二级结构元件之间内部接触表面的残基通常不变，如Phe-12、Val-25和Phe-27。
