ASSOC/FOLDING PROCESSES OF THIOREDOXIN FRAGMENT

描述：蛋白质结构的预测完全基于 它们的一级序列，设计具有所需 性质，以及从包涵体中重折叠蛋白质，都需要 对形成的基本原则有清晰的理解， α-螺旋和β-折叠的组装。 取得了进展 确定每种氨基酸形成α-螺旋的倾向， 也用于从头设计α-螺旋肽和蛋白质。 但是，在这方面， 对β-折叠形成的理解 成功 Tasayco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 仍然很少了解的β-折叠使用协会/折叠 混合α β硫氧还蛋白互补片段之间的过程 蛋白质作为模型系统。 了解这种结构的折叠 基序，本质上重要的氧化-氧化还原系统，将提供 合理设计具有所需药理学活性的分子的基础 特性. Tasayco博士的方法是研究四个选定的互补 蛋白质片段，并将其与完整蛋白质进行比较。 她建议 解剖E.大肠杆菌硫氧还蛋白片段。 这些碎片将被 其特征在于使用生物化学和生物物理工具的组合， 增加结构细节。 她将利用圆二色性 远、近紫外、荧光、多维核磁 共振光谱和计算机建模。 这项工作将组织起来 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）。 目标二。 研究 非共价复合物的结构、稳定性和动力学（1-37和 38-108、1-37、38-73和74-108）。 目标3： 折叠的比较 重组的完整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.