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ASSOC/FOLDING PROCESSES OF THIOREDOXIN FRAGMENT

硫氧还蛋白片段的关联/折叠过程

基本信息

批准号：
6181255
负责人：
MARIA L TASAYCO
金额：
$ 3.93万
依托单位：
CITY COLLEGE OF NEW YORK
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-30 至 2001-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6181255
关键词：
circular dichroism computer simulation molecular dynamics nuclear magnetic resonance spectroscopy protein folding protein structure function thioredoxin

项目摘要

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.

描述：仅基于蛋白质结构的预测他们的一级序列，具有所需的从头蛋白质的设计特性，以及蛋白质从包涵体的重折叠，都需要清楚地了解形成和形成的基本原则 α-螺旋和β-折叠的组装。已取得进展确定每种氨基酸形成 α 螺旋的倾向，还涉及从头 α 螺旋肽和蛋白质的设计。然而，对β-折叠形成的理解较少成功。 Tasayco 博士研究的长期目标是了解如何蛋白质结构控制功能。该提案的目的是了解结构、稳定性、动力学和折叠之间的关系使用关联/折叠来了解仍然知之甚少的β-sheet 混合αβ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对于氧化-氧化还原系统本质上很重要的基序将提供合理设计具有所需药理作用的分子的基础特性。 Tasayco 博士的方法是研究四种选定的互补蛋白质片段并将其与完整蛋白质进行比较。她提议将大肠杆菌硫氧还蛋白解剖成片段。这些片段将是使用生物化学和生物物理工具的组合进行表征结构细节水平不断提高。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。将组织开展工作围绕三个具体目标：目标 1. 结构和稳定性研究分离片段（1-37、38-73、38-108、74-108）。目标 2. 研究非共价配合物（1-37 和 38-108、1-37、38-73 和 74-108）。目标3. 之间的折叠比较重组且完整的 Trx。