The crystal structure of the liver fatty acid-binding protein - A complex with two bound oleates
The crystal structure of the liver fatty acid-binding protein - A complex with two bound oleates
复制标题
DOI：
10.1074/jbc.272.11.7140
复制
发表时间：
1997-03-14
影响因子：
4.8
通讯作者：
Banaszak, L
中科院分区：
文献类型：
--
作者：
Thompson, J;Winter, N;Banaszak, L
重组大鼠肝脏脂肪酸结合蛋白的晶体结构达到2.3埃，精制后的R因子为19.0%。以6个细胞内脂结合蛋白的聚丙氨酸坐标为搜索探针，通过分子置换获得结构溶液。在晶体结构中模拟了大鼠肝脏脂肪酸结合蛋白的整个氨基酸序列以及氨基末端的甲酰蛋氨酸。此外，该晶体是在油酸存在的情况下获得的，初始电子密度清楚地显示两个脂肪酸分子结合在一个中心空腔内。一个脂肪酸分子的羧酸盐与精氨酸122相互作用，不受游离溶剂的影响，它具有整体的弯曲构象。另一种油酸盐中溶剂暴露较多的羧酸盐位于覆盖贝塔桶一端的螺旋转角螺旋附近，而酰基链位于内部。空腔中既有极性残基，也有非极性残基，但在配体的非极性原子周围也表现出广泛的疏水特性。初级和次级油酸结合位点似乎完全相互依赖，主要是因为在两个脂肪链之间形成了有利的疏水相互作用。
The crystal structure of the recombinant form of rat liver fatty acid binding protein was completed to 2.3 Angstrom and refined to an R factor of 19.0%. The structural solution was obtained by molecular replacement using superimposed polyalanine coordinates of six intracellular lipid binding proteins as a search probe. The entire amino acid sequence of rat liver fatty acid-binding protein along with an amino-terminal formyl-methionine was modeled in the crystal structure. In addition, the crystal was obtained in the presence of oleic acid, and the initial electron density clearly showed two fatty acid molecules bound within a central cavity. The carboxylate of one fatty acid molecule interacts with arginine 122 and is shielded from free solvent, It has an overall bent conformation. The more solvent-exposed carboxylate of the other oleate is located near the helix-turn-helix that caps one end of the beta-barrel, while the acyl chain lies in the interior. The cavity contains both polar and nonpolar residues but also shows extensive hydrophobic character around the nonpolar atoms of the ligands. The primary and secondary oleate binding sites appear to be totally interdependent, mainly because favorable hydrophobic interactions form between both aliphatic chains.