ACQUISITION OF A 500 MHZ NMR CONSOLE

该子项目是利用由NIH/NCRR资助的共享仪器赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是用于资助的，不一定是研究者的机构。描述（由申请人提供）：虽然蛋白质结构的独特性和稳定性至关重要，但这种结构的变化对于结合和催化作用至关重要。现在很明显，许多蛋白质的识别过程中纳入构象变化作为一个必要的事件的功能。以这种方式，蛋白质结构和动力学通过大尺度和小尺度构象波动与生物活性密切相关。在加州大学圣地亚哥分校化学和生物化学系的Jennings，Opella，Taylor，Handel和Komives实验室的研究工作通常是针对理解蛋白质和肽折叠，分子识别和与功能调节相关的构象开关的动力学。我们每个研究项目的一个关键要素是使用高分辨率NMR方法进行结构解析，探测蛋白质/配体识别机制，理解折叠反应和表征天然肽/蛋白质动力学。我们每个实验室研究进展的一个主要障碍是，光谱仪时间的高需求限制了对部门仪器的访问。目前，部门生物分子NMR光谱仪的典型等待时间为2 1/2 - 3个月。我们正在申请资金，为我们的500 MHz Varian Unity NMR光谱仪购买一个现代化的控制台。有了新的控制台，光谱仪将能够进行全方位的多维NMR实验，用于同位素标记的肽和蛋白质的研究。用具有全PFG功能的新控制台取代单独的控制台，并为仪器配备三重共振三轴梯度探头，将大大加强我们每个实验室和部门的研究工作，允许实施和发展现代脉冲序列，并为要求苛刻的应用提供更高的灵敏度，如分析微溶蛋白质和肽。

This subproject is one of many research subprojects utilizing the resources provided by a Shared Instrumentation 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 grant, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): While it is critical for a protein's structure to be unique and stable, changes in this structure are imperative for binding and catalysis. It is now evident that many protein recognition processes incorporate conformational changes as a requisite event for function. In this manner, protein structure and dynamics are intimately linked with biological activity via both large and small scale conformational fluctuations. Research efforts in the Jennings, Opella, Taylor, Handel, and Komives laboratories in the Department of Chemistry and Biochemistry at UCSD are directed, in general towards understanding the dynamics of protein and peptide folding, molecular recognition and the conformational switches that correlate the regulation of function. A key element in each of our research programs is the use of high-resolution NMR methods for structure elucidation, probing protein/ligand recognition mechanisms, understanding folding reactions and characterizing native peptide/protein dynamics. A major impediment to research progress in each of our laboratories is the fact that access to departmental instruments is restricted by the high demand of spectrometer time. Currently, the typical waiting time on the departmental biomolecular NMR spectrometers is 2 1/2 - 3 months. We are requesting funds for the purchase of a modern console for our 500 MHz Varian Unity NMR spectrometer. With a new console, the spectrometer will be capable of the full range of multidimensional NMR experiments for studies of isotopically labeled peptides and proteins. The replacement of solely the console with a new console with full PFG capabilities and equipping the instrument with a triple-resonance triple axis gradient probe will significantly enhance research efforts in each of our laboratories and the Department by allowing implementation and development of modern pulse sequences as well as affording enhanced sensitivity for demanding applications such as analysis of marginally soluble proteins and peptides.