ASSOC/FOLDING PROCESSES OF THIOREDOXIN FRAGMENT

描述：对蛋白质结构的预测仅基于 它们的初级序列，与所需的从头蛋白的设计 性质，以及从包涵体中重新折叠蛋白质，都需要 对形成和发展的基本原则有一个清晰的理解 α-螺旋和β-折叠的组装。在以下方面取得了进展 确定每种氨基酸形成α-螺旋的倾向和 在设计新的α-螺旋多肽和蛋白质时也是如此。然而， 对于β-折叠的形成，人们的理解还很少。 成功。塔萨伊科博士研究的长期目标是了解 蛋白质结构决定功能。这项建议的目的是 理解结构、稳定性、动力学和折叠之间的关系 使用关联/折叠的仍鲜为人知的测试页 混合α-β硫氧还蛋白互补片段间的相互作用 蛋白质作为一个模型系统。了解这一结构的折叠 Motif对于氧化-氧化还原系统至关重要，它将提供 合理设计具有理想药理作用的分子的基础 属性。Tasayco博士的方法是研究选定的四个互补的 蛋白质片段，并与完整的蛋白质进行比较。她提议 将大肠杆菌硫氧还蛋白解剖成碎片。这些碎片将会是 使用生化和生物物理工具的组合来表征的 提高了结构细节的级别。她将使用圆二向色性 远、近紫外、荧光、多维核磁 共振光谱学和计算机建模。这项工作将是有组织的 围绕三个具体目标：目标1.结构和稳定性研究 分离的片段(1-37、38-73、38-108、74-108)。目标2.研究 非共价络合物(1-37和 38-108、1-37、38-73和74-108)。目标3.两种折叠方式的比较 重组的和完整的Trx。

DESCRIPTION: The prediction of the structure of proteins based solely on their primary sequence, the design of denovo proteins with desired properties, and the refolding of proteins from inclusion bodies, all require a clear understanding of the principles underlying the formation and assembly of alpha-helices and beta-sheets. Progress has been made in establishing the propensity of each amino acid to form alpha-helices and also in the design of denovo alpha-helical peptides and proteins. However, the understanding of the formation of beta-sheets has been met with less success. The long term goal of Dr. Tasayco's research is to understand how protein structure governs function. The objective of this proposal is to understand the relationship among structure, stability, dynamics and folding of the still little understood beta-sheets using the association/folding process between complementary fragments of the mixed alpha beta thioredoxin protein as a model system. Understanding the folding of this structural motif, intrinsically important for the oxi-redox system, will provide the basis for the rational design of molecules with desired pharmacological properties. Dr. Tasayco's approach is to study four selected complementary protein fragments and compare them with the intact protein. She proposes to dissect E. coli thioredoxin into fragments. These fragments will be characterized using a combination of biochemical and biophysical tools with increasing level of structural detail. She will use circular dichroism in the far and near UV, fluorescence, multidimensional nuclear magnetic resonance spectroscopy and computer modeling. The work will be organized around three specific aims: Aim 1. Studies of the structure and stability of the isolated fragments (1-37, 38-73, 38-108, 74-108). Aim 2. Studies of the structure, stability and dynamics of non-covalent complexes (1-37 and 38-108, 1-37, 38-73 and 74-108). Aim 3. Comparison of the folding between the reconstituted and intact Trx.