NMR METHODOLOGY FOR CHARACTERIZING CARBOHYDRATE-PROTEIN INTERACTIONS (TB1)

表征碳水化合物-蛋白质相互作用的 NMR 方法 (TB1)

• 批准号: 8361784
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 10.63万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361784
• 关键词: Carbohydrates; Cell Aggregation; Cell Differentiation process; Cells; Data; Disease; Environment; Funding; Glycosaminoglycans; Grant; Inflammation; Isotopes; Label; Laboratories; Malignant Neoplasms; Methodology; Methods; Modeling; National Center for Research Resources; Nuclear Magnetic Resonance; Oligosaccharides; Physiological Processes; Principal Investigator; Process; Protein-Carbohydrate Interaction; Proteins; Research; Research Infrastructure; Resolution; Resources; Retrieval; Signal Transduction; Source; Structural Models; System; Technology; United States National Institutes of Health; Virus Diseases; chemokine; cost; drug development; protein complex; research study; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project is part of a more general integrated technology project directed at the structural characterization of glycoaminoglycan-protein complexes. The formation of carbohydrate-protein complexes, in general, is important in a variety of processes involving the interaction of a cell with its environment. These processes include physiological processes, such as cell differentiation, cell aggregation, and cell signaling; they also include disease processes, such as viral infection, malignancy, and unwanted inflammation. The development of drugs to moderate natural processes and inhibit disease processes begins with accurate structural models for oligosaccharide-protein interactions. These models have been difficult to get by traditional Nuclear Magnetic Resonance (NMR) approaches because of the dearth of short-distance NOE contacts in oligosaccharide-protein complexes. We are developing a number of experiments and analysis tools that allow retrieval of structural information when traditional NMR approaches fail. This particular project combines new isotopic labeling strategies developed in the Moremen laboratory with new methods of assignment, and new types of NMR-observable structural data. The target systems include both glycosylated proteins that are difficult to express in forms amenable to use of NMR strategies that are dependent on uniform labeling with multiple NMR-active isotopes, and high order aggregates including chemokine-glycosaminoglycan (GAG) aggregates, where resolution and sensitivity become a problem.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该项目是针对糖胺聚糖-蛋白质复合物结构表征的更通用综合技术项目的一部分。 一般来说，碳水化合物-蛋白质复合物的形成在涉及细胞与其环境相互作用的各种过程中很重要。这些过程包括生理过程，例如细胞分化、细胞聚集和细胞信号传导；它们还包括疾病过程，例如病毒感染、恶性肿瘤和不必要的炎症。缓和自然过程和抑制疾病过程的药物的开发始于寡糖-蛋白质相互作用的精确结构模型。由于寡糖-蛋白质复合物中缺乏短距离 NOE 接触，因此传统的核磁共振 (NMR) 方法很难获得这些模型。我们正在开发许多实验和分析工具，以便在传统核磁共振方法失败时检索结构信息。这个特殊项目将 Moremen 实验室开发的新同位素标记策略与新的分配方法以及新型 NMR 可观察结构数据相结合。 目标系统包括难以以适合使用 NMR 策略的形式表达的糖基化蛋白质，这些策略依赖于多种 NMR 活性同位素的统一标记，以及包括趋化因子-糖胺聚糖 (GAG) 聚集体在内的高阶聚集体，其中分辨率和灵敏度成为一个问题。