Three-dimensional structure of recombinant human muscle fatty acid-binding protein.
Three-dimensional structure of recombinant human muscle fatty acid-binding protein.
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DOI：
10.2210/pdb2hmb/pdb
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发表时间：
1994-01
期刊：
影响因子：
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通讯作者：
Giuseppe Zanotti;Giovanna Scapin;P. Spadon;Jacques H. Veerkamp;J. C. Sacchettini
中科院分区：
文献类型：
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作者：
Giuseppe Zanotti;Giovanna Scapin;P. Spadon;Jacques H. Veerkamp;J. C. Sacchettini
具有结合脂肪酸的重组人肌肉脂肪酸结合蛋白的三维结构已通过 X 射线衍射数据解析并细化至 2.1 A 分辨率。对于 9.0 和 2.1 A 之间的数据（7243 个独特反射），精炼模型的晶体学 R 因子为 19.5%，键长和键角的均方根偏差为 0.013 A 和 2.7 度。该蛋白质含有 10 个反向平行的 β 链和两个短的 α 螺旋，它们排列成两个近似正交的 β 折叠。差异电子密度图和多重同晶导数电子密度图显示蛋白质内部核心内存在长链脂肪酸的单个结合分子。发现脂肪酸的烃尾部呈“U形”构象。在脂肪酸弯曲的碳氢化合物尾巴的伪硅面上的一个口袋中的蛋白质内部还鉴定出了七个有序的水分子。脂肪酸的亚甲基尾部与来自 13 个残基和三个有序水的原子形成范德华相互作用。脂肪酸的羧酸盐位于蛋白质的内部，与 Tyr128 和 Arg126 的侧链以及两个有序水分子形成氢键。人肌肉脂肪酸结合蛋白和大鼠肠脂肪酸结合蛋白的三维结构比较显示出很强的相似性。两种蛋白质都在其内部核心内结合单个脂肪酸，但结合的脂肪酸在构象和相互作用方面非常不同。这些发现表明，肠道和肌肉脂肪酸结合蛋白已经进化出不同的结合位点，以满足它们表达的组织内的不同需求。
The three-dimensional structure of recombinant human muscle fatty acid-binding protein with a bound fatty acid has been solved and refined with x-ray diffraction data to 2.1 A resolution. The refined model has a crystallographic R factor of 19.5% for data between 9.0 and 2.1 A (7243 unique reflections) and root-mean-square deviations in bond length and bond angle of 0.013 A and 2.7 degrees. The protein contains 10 antiparallel beta-strands and two short alpha-helices which are arranged into two approximately orthogonal beta-sheets. Difference electron density maps and a multiple isomorphous derivative electron density map showed the presence of a single bound molecule of a long chain fatty acid within the interior core of the protein. The hydrocarbon tail of the fatty acid was found to be in a "U-shaped" conformation. Seven ordered water molecules were also identified within the interior of the protein in a pocket on the pseudo-si face of the fatty acid's bent hydrocarbon tail. The methylene tail of the fatty acid forms van der Waals interactions with atoms from 13 residues and three ordered waters. The carboxylate of the fatty acid is located in the interior of the protein where it forms hydrogen bonds with the side chains of Tyr128 and Arg126 and two ordered water molecules. A comparison of the three-dimensional structure of human muscle fatty acid-binding protein and rat intestinal fatty acid-binding protein shows strong similarity. Both proteins bind a single fatty acid within their interior cores, but the bound fatty acids are very different in their conformations and interactions. These findings suggest that the intestinal and muscle fatty acid-binding proteins have evolved distinct binding sites in order to satisfy different requirements within the tissues where they are expressed.