STRUCTURAL STUDIES ON HUMAN MUSCLE FATTY-ACID-BINDING PROTEIN AT 1.4-ANGSTROM RESOLUTION - BINDING INTERACTIONS WITH 3 C18 FATTY-ACIDS
STRUCTURAL STUDIES ON HUMAN MUSCLE FATTY-ACID-BINDING PROTEIN AT 1.4-ANGSTROM RESOLUTION - BINDING INTERACTIONS WITH 3 C18 FATTY-ACIDS
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DOI：
10.1016/s0969-2126(00)00052-6
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发表时间：
1994-06-15
期刊：
影响因子：
5.7
通讯作者：
SACCHETTINI, JC
中科院分区：
文献类型：
--
作者：
YOUNG, ACM;SCAPIN, G;SACCHETTINI, JC
背景：肌肉脂肪酸结合蛋白（M-FABP）是参与脂肪酸加工的胞质脂质结合蛋白家族之一。为了研究M-FABP与其配体之间的精确相互作用，并了解差异结合亲和力的结构基础，我们比较了M-FABP与三种C18脂肪酸复合物的结构。结果：我们描述了M-FABP与正十八烷酸酯（硬脂酸酯）、反式Delta（9）-十八烯酸酯（反式）和顺式Delta（9）-十八烯酸酯（油酸酯）复合物的晶体结构。对于分辨率在 8.0 埃到 1.4 埃之间的所有数据，使用最小二乘位置和各向异性温度因子精炼对这些结构进行精炼，最终 R 因子分别为 11.4 %、12.1 % 和 13.2 %。结论：当硬脂酸盐、反油酸盐和油酸盐在大的内部结合腔内与 M-FABP 结合时，它们各自采用高度相似的 U 形构象，其中还包含13个有序水分子。无论结合配体的性质如何，蛋白质的原子结构实际上是相同的。脂肪酸被认为通过其表面的入口进入蛋白质的内部空腔，而内部溶剂通过第二个开口释放。配体亲和力可以与结合配体的构象能和溶解度相关。
Background: Muscle fatty acid binding protein (M-FABP) is one of a family of cytosolic lipid-binding proteins involved in fatty acid processing. In order to investigate the precise interactions between M-FABP and its ligands and to understand the structural basis of differential binding affinity, we have compared the structures of M-FABP in complex with three C18 fatty acids.Results: We describe the crystal structures of M-FABP in complex with n-octadecanoate (stearate), trans Delta(9)-octadecenoate (elaidate) and cis-Delta(9)-octadecenoate (oleate). These structures were refined using least-squares positional and anisotropic temperature factor refinement to final R-factors of 11.4 %, 12.1 % and 13.2 % respectively for all the data between 8.0 Angstrom and 1.4 Angstrom resolution.Conclusions: Stearate, elaidate and oleate each adopt highly similar U-shaped conformations when they bind to M-FABP within a large interior binding cavity, which also contains 13 ordered water molecules. The atomic structure of the protein is virtually identical, regardless of the nature of the bound ligand. The fatty acid is thought to enter the interior cavity of the protein via a portal in its surface while interior solvent is released through a secondary opening. The ligand affinity can be correlated with the conformational energy and the solubility of the bound ligand.