Probing the Fibrate Binding Specificity of Rat Liver Fatty Acid Binding Protein
Probing the Fibrate Binding Specificity of Rat Liver Fatty Acid Binding Protein
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DOI：
10.1021/jm801349e
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发表时间：
2009-09-10
影响因子：
7.3
通讯作者：
Scanlon, Martin J.
中科院分区：
文献类型：
--
作者：
Chuang, Sara;Velkov, Tony;Scanlon, Martin J.
肝脂肪酸结合蛋白（L-FABP）在肠细胞中含量很高，参与脂肪酸的胞质溶解。此外，L-FABP已被证明与内源性和外源性亲脂化合物结合，表明它也可能在调节它们在肠细胞内的吸收和处置中发挥作用。以前，我们已经描述了L-FABP与一系列药物的结合，包括一系列贝特类药物。在本研究中，我们建立了l - fabp -贝特酸酯复合物的结构模型，并对含有羧酸或酯功能的贝特酸酯结合进行了热力学分析。对现有数据的分析表明，与不含羧酸盐的贝特酸盐相比，含有羧酸盐的贝特酸盐的结合位置和能量学都不同。因此，本研究提供的数据提示了支持分子识别的潜在机制，并决定了贝特酸盐和L-FABP之间相互作用的特异性。
Liver-fatty acid binding protein (L-FABP) is found in high levels in enterocytes and is involved in cytosolic solubilization of fatty acids. In addition, L-FABP has been shown to bind endogenous and exogenous lipophilic compounds, suggesting that it may also play a role in modulating their absorption and disposition within enterocytes. Previously, we have described binding of L-FABP to a range of drugs, including a series of fibrates. In the present study, we have generated structural models of L-FABP-fibrate complexes and undertaken thermodynamic analysis of the binding of fibrates containing either a carboxylic acid or ester functionality. Analysis of the current data reveals that both the location and the energetics of binding are different for fibrates that contain a carboxylate compared to those that do not. As such, the data presented in this study suggest potential mechanisms that underpin molecular recognition and dictate specificity in the interaction between fibrates and L-FABP.