Young A C, Scapin G, Kromminga A, Patel S B, Veerkamp J H, Sacchettini J C
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461.
Structure. 1994 Jun 15;2(6):523-34. doi: 10.1016/s0969-2126(00)00052-6.
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.
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 A and 1.4 A resolution.
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.
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。
我们描述了M-FABP与正十八烷酸（硬脂酸）、反式Δ9-十八碳烯酸（反油酸）和顺式Δ9-十八碳烯酸（油酸）复合物的晶体结构。使用最小二乘法位置和各向异性温度因子精修对这些结构进行精修，对于8.0 Å至1.4 Å分辨率之间的所有数据，最终的R因子分别为11.4%、12.1%和13.2%。
当硬脂酸、反油酸和油酸在一个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，该腔内还包含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一个入口进入蛋白质的内部腔，而内部溶剂则通过一个二级开口释放。配体亲和力可与结合配体的构象能和溶解度相关联。
