FLUORESCENCE STUDIES OF FATTY ACID BINDING PROTEINS

描述：脂肪酸结合蛋白(FABP)是一个小分子家族。 胞浆蛋白在各种组织和许多组织中大量存在 有机体。FABP很可能在运输中扮演着重要的角色 和脂肪酸的新陈代谢。在这种情况下，这些蛋白质的变化 可能与脂肪代谢相关的疾病有关， 事实上，最近的证据表明，肠道FABP的修饰可能 与糖尿病有关。因为有相当多的氨基酸序列 不同组织中FABP的差异人们普遍认为 这些蛋白质的生化特性将是组织特有的，但 直到最近，还没有证据证明这种可变性。在过去 然而，三年来，我们的研究表明，热力学 FA-FABP相互作用的动力学性质非常敏感 与FABP的组织起源和FA的分子物种有关。 本研究的长期目标是(1)提供严格的 了解这些蛋白质的生理作用的生化基础， (2)了解导致观察到的 组织特异性结合的异质性，以及(3)发展各种 游离脂肪酸(FFA)荧光探针在生物化学中的应用 临床医学和生物化学。 因为FABP可以根据它们的序列同源性和我们的 对其中三个基团的初步研究揭示了热力学特征 是这些基团的特征，他将首先扩展这些 向其他小组的成员提供各种研究。对于其中的每一个组 然后我们将使用定点突变来改变氨基酸残基， 在结合腔内相互作用并确定相互作用能 对应于每一次残基变化。最后，他将使用以下结果 这些研究旨在构建具有新的结合和荧光的新型FFA探针 光谱性质。

DESCRIPTION: Fatty acid binding proteins (FABP) are a family of small cytosolic proteins that are abundant in a variety of tissues and in many organisms. It is likely that FABPs play important roles in the transport and metabolism of fatty acids. In this event alterations in these proteins might be involved in diseases in which fat metabolism is implicated and indeed recent evidence suggests that modification of the intestinal FABP may be linked to diabetes. Because there is considerable amino acid sequence variation in FABPs from different tissues it has generally been thought that the biochemical properties of these proteins would be tissue specific, yet until recently no evidence existed for such variability. During the past three years, however, our studies have demonstrated that the thermodynamic and kinetic properties of FA-FABP interactions are extremely sensitive both to the tissue origin of the FABP and to the molecular species of FA. The long-term goals of the present studies are (1) to provide a rigorous biochemical basis for understanding the physiologic role of these proteins, (2) to understand the molecular interactions that give rise to the observed tissue-specific heterogeneity of binding, and (3) to develop a variety of fluorescent probes of free fatty acids (FFA) that will have application in clinical medicine as well as biochemistry. Because FABPs can be grouped according to their sequence homologies and our initial studies of three of these groups reveal that thermodynamic features of FA binding are characteristic of these groups, he will first extend these kinds of studies to members of other groups. For each one of these groups we will then use site directed mutagenesis to alter amino acid residues that interact in the binding cavity and determine the interaction energies corresponding to each residue change. Finally, he will use the results of these studies to construct new FFA probes with novel binding and fluorescent spectroscopic properties.