Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland.
Institute of Microbiology and Genetics, Department for Molecular Structural Biology, GZMB, Justus-von-Liebig Weg 11, 37077 Göttingen, Germany.
Acta Crystallogr D Struct Biol. 2017 Nov 1;73(Pt 11):896-909. doi: 10.1107/S205979831701470X. Epub 2017 Oct 25.
Serum albumin (SA) is the most abundant protein in plasma and is the main transporter of molecules in the circulatory system of all vertebrates, with applications in medicine, the pharmaceutical industry and molecular biology. It is known that albumins from different organisms vary in sequence; thus, it is important to know the impact of the amino-acid sequence on the three-dimensional structure and ligand-binding properties. Here, crystal structures of ovine (OSA) and caprine (CSA) serum albumins, isolated from sheep and goat blood, are described, as well those of their complexes with 3,5-diiodosalicylic acid (DIS): OSA-DIS (2.20 Å resolution) and CSA-DIS (1.78 Å resolution). The ligand-free OSA structure was determined in the trigonal space group P321 at 2.30 Å resolution, while that of CSA in the orthorhombic space group P222 was determined at 1.94 Å resolution. Both albumins are also capable of crystallizing in the triclinic space group P1, giving isostructural crystals that diffract to around 2.5 Å resolution. A comparison of OSA and CSA with the closely related bovine serum albumin (BSA) shows both similarities and differences in the distribution of DIS binding sites. The investigated serum albumins from domesticated ruminants in their complexes with DIS are also compared with the analogous structures of equine and human serum albumins (ESA-DIS and HSA-DIS). Surprisingly, despite 98% sequence similarity, OSA binds only two molecules of DIS, whereas CSA binds six molecules of this ligand. Moreover, the binding of DIS to OSA and CSA introduced changes in the overall architecture of the proteins, causing not only different conformations of the amino-acid side chains in the binding pockets, but also a significant shift of the whole helices, changing the volume of the binding cavities.
血清白蛋白（SA）是血浆中含量最丰富的蛋白质，也是所有脊椎动物循环系统中分子的主要转运蛋白，在医学、制药工业和分子生物学中有广泛的应用。已知不同生物体的白蛋白在序列上有所不同；因此，了解氨基酸序列对三维结构和配体结合特性的影响是很重要的。本文描述了来自绵羊和山羊血液的绵羊（OSA）和山羊（CSA）血清白蛋白及其与 3,5-二碘水杨酸（DIS）复合物的晶体结构：OSA-DIS（2.20 Å 分辨率）和 CSA-DIS（1.78 Å 分辨率）。无配体的 OSA 结构在三角空间群 P321 中以 2.30 Å 的分辨率确定，而 CSA 在正交空间群 P222 中以 1.94 Å 的分辨率确定。这两种白蛋白也能够在三斜空间群 P1 中结晶，得到结构相同的晶体，可衍射至约 2.5 Å 的分辨率。OSA 和 CSA 与密切相关的牛血清白蛋白（BSA）的比较显示，DIS 结合位点的分布既有相似之处，也有不同之处。本文还比较了来自家养反刍动物的研究血清白蛋白与其 DIS 复合物与马和人血清白蛋白（ESA-DIS 和 HSA-DIS）的类似结构。令人惊讶的是，尽管序列相似度为 98%，但 OSA 仅结合两个 DIS 分子，而 CSA 结合六个 DIS 分子。此外，DIS 与 OSA 和 CSA 的结合导致蛋白质整体结构发生变化，不仅使结合口袋中氨基酸侧链的构象发生不同，而且整个螺旋也发生明显移位，改变了结合腔的体积。
