STRUCTURAL CHARACTERIZATION OF THE DIFFERENT DOMAINS OF THE ALPHA ISOFORM OF

α亚型不同域的结构特征

• 批准号: 7726020
• 负责人: Shyamala Rajan
• 金额: $ 0.79万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726020
• 关键词: Chimeric Proteins; Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; Data Set; Estrogen Receptors; Evaluation; Funding; Grant; Human; Institution; Knowledge; Length; Ligand Binding Domain; Protein Isoforms; Proteins; Research; Research Personnel; Resources; Source; Therapeutic; Time; United States National Institutes of Health; Work; maltose-binding protein; mutant; novel; scaffold; small molecule; therapeutic target

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This proposal is part of our ongoing structural studies aimed at the characterization of all the domains of the hER, biochemically important mutants of these domains, and evaluation of potential therapeutic targets. We have been working on the structural characterization of the human Estrogen Receptor (hER) ligand binding domain (LBD) complexes with potential therapeutic small molecules since the Spring of 2005. These compounds have encompassed those with novel scaffolds, varying potency and selectivity for the different isoforms of hER. We have recently begun to characterize the other domains of hERalpha (besides the LBD). We have obtained crystals of A though D domains of both the wild type and point mutant proteins expressed as fusion products with the maltose binding protein (MBP). These MBP fusion proteins are soluble and have crystallized in several conditions of our intial screens. This is exciting progress because we have no structural knowledge to date, of the three dimensional organization of the various domains of hER. We need beam time to screen these crystals of various length of hER for diffraction quality, so we can optimize the conditions for better crystals. We also hope to collect a few datasets.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该提案是我们正在进行的结构研究的一部分，旨在表征 hER 的所有结构域、这些结构域的生化重要突变体以及潜在治疗靶点的评估。自 2005 年春季以来，我们一直致力于人类雌激素受体 (hER) 配体结合域 (LBD) 复合物与潜在治疗性小分子的结构表征。这些化合物涵盖了具有新颖支架、对不同 hER 亚型具有不同效力和选择性的化合物。我们最近开始表征 hERalpha 的其他结构域（除了 LBD）。我们已经获得了野生型和点突变蛋白的 A 至 D 结构域晶体，它们表达为与麦芽糖结合蛋白 (MBP) 的融合产物。这些 MBP 融合蛋白是可溶的，并且在我们初步筛选的几种条件下已经结晶。这是令人兴奋的进展，因为迄今为止我们还没有 hER 各个领域的三维组织的结构知识。我们需要光束时间来筛选这些不同长度 hER 晶体的衍射质量，因此我们可以优化条件以获得更好的晶体。我们还希望收集一些数据集。