Defining the conformational control of nitric oxide synthases by a multipronged approach

通过多管齐下的方法定义一氧化氮合酶的构象控制

• 批准号: 10385652
• 负责人: Changjian Feng
• 金额: $ 10.5万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385652
• 关键词: Administrative Supplement; Alzheimer' s Disease; Anabolism; Award; Bioinorganic Chemistry; Complex Mixtures; Development; Disease; Environment; Equipment; Family; Financial Support; Funding; Institution; Investments; Laboratories; Lead; Liquid Chromatography; Methods; Molecular Conformation; Multienzyme Complexes; New Mexico; Nitric Oxide; Nitric Oxide Synthase; Parents; Pharmacy facility; Process; Production; Productivity; Proteins; Research; Research Personnel; Site; Stroke; System; Techniques; United States National Institutes of Health; Universities; Work; biophysical chemistry; college; effective therapy; fast protein liquid chromatography; instrumentation; milligram; novel therapeutic intervention; novel therapeutics; parent project; programs; protein complex; protein purification; spectroscopic survey; unnatural amino acids

PROJECT SUMMARY The parent award is on deciphering conformational dynamics of nitric oxide synthase proteins through an integrated approach using advanced spectroscopic techniques. Detailed spectroscopic studies require milligram amounts of highly purified protein. Fast protein liquid chromatography (FPLC) is a form of liquid chromatography used to purify a target protein from a complex mixture. Our current FPLC has been a workhorse, but is near the end of operational lifetime. This administrative supplement is being requested to allow acquisition of a state-of-the-art ÄKTA pure 25 system. It has direct relevance to and immediate utility in enhancing our laboratory’s protein purification capabilities. As such, this equipment will greatly enhance our research productivity for the duration of the project, and will help us maintain a strong research program. Importantly, the unique capabilities of the ÄKTA pure 25 system will be indispensable for our efforts to develop and optimize methods for site-specifically incorporating unnatural amino acids into large, complex proteins with high fidelity, yield, and purity. Our findings will therefore be of great utility for other investigators using this process for other large, complex enzymes. Therefore, the requested equipment will help the parent project to exert a sustained, powerful influence on the research fields of bioinorganic and biophysical chemistry. Moreover, the administrative supplement will enhance the scientific environment for NIH-funded investigators at the University of New Mexico, both within and outside of the College of Pharmacy. To our knowledge, no comparable instrumentation exists in educational institutions within the region. Dean Godwin has committed substantial financial support to this supplement request since this is a great investment for the College. Taken as a whole, the proposed supplement will increase the parent award’s overall impact within the original scope of award, as well as bolster research quality and depth at our institution.

项目概要 家长奖是通过破译一氧化氮合酶蛋白的构象动力学 使用先进光谱技术的综合方法需要详细的光谱研究。 毫克量的高纯度蛋白质快速蛋白质液相色谱 (FPLC) 是液体的一种形式。 我们目前的 FPLC 是用于从复杂混合物中纯化目标蛋白的色谱法。 主力，但已接近运行寿命结束，正在请求此行政补充。 允许购买最先进的 AKTA pure 25 系统，它与以下领域有直接相关性和直接实用性。 增强我们实验室的蛋白质纯化能力 因此，该设备将极大地增强我们的实验室。 项目期间的研究生产力，并将帮助我们保持强大的研究计划。 重要的是，AKTA pure 25 系统的独特功能对于我们的开发工作是不可或缺的 并优化将非天然氨基酸定点整合到大型复杂蛋白质中的方法 因此，我们的研究结果对于其他使用该方法的研究人员来说非常有用。 因此，所需的设备将有助于母项目 对生物无机化学和生物物理化学研究领域产生了持续、强大的影响。 此外，行政补充将改善 NIH 资助的研究人员的科学环境 在新墨西哥大学药学院内外，据我们所知，没有。 Dean Godwin 承诺该地区的教育机构中存在类似的仪器。 对该补充请求提供大量财政支持，因为这对学院来说是一笔巨大的投资。 总体而言，拟议的补充将在原有范围内增加家长奖励的整体影响 奖项，以及支持我们机构的研究质量和深度。