600 MHz Nuclear Magnetic Resonance Spectrometer

描述（由申请人提供）：需要一台高场多核核磁共振光谱仪来支持马奎特大学和密尔沃基地区新的和正在进行的项目。拟议的工具将支持和扩展现有的NIH和其他资助项目，为3个机构的6个主要用户和4个次要用户提供服务。主要用户组由8个NIH拨款资助，次要用户由各种来源资助。主要用户参与的项目直接针对生物化学中的问题，这些问题主要使用NMR，而次要用户的项目主要依赖NMR作为辅助角色。为了研究蛋白质-配体相互作用，光谱仪的一个关键特征是在600兆赫下具有高灵敏度和高分辨率。核磁共振设施将提供多种探针选择，包括MicroFlow和BB，从而满足其他设施无法满足的区域需求。项目包括：(1)在化学蛋白质组学中探测蛋白质-配体相互作用：核磁共振方法的开发和应用（Sem）；(2)利用核磁共振和拉曼的互补研究来探测配体与细胞色素P450cam的结合（Kincaid）； (3) Fi-Fo ATP合成酶二聚体的苏e信息的作用：结构和结合研究（Stuart）；(4)鞭毛径向辐的机制；径向辐状蛋白2 （RSP2）的配体结合和结构研究（Yang）； (5) nadph依赖性细胞色素P450氧化还原酶（Kim）分子运动的结构表征；(6)Fell依赖性非血红素加氧酶的顺磁弛缓和异核相关的底物结合几何形状（Moran）。该光谱仪是“马奎特化学蛋白质组学设施”的核心部件，因此得到了马奎特大学的大力支持，除了要求的50万美元之外，马奎特大学还承诺提供额外的368,945美元，以及所需的空间、设施、人员、冷冻器、保修和其他支持。虽然邻近的核磁共振设施目前正在使用，但它们不能满足现有的需求，主要原因是需要100英里的行程和常规高场实验的提前安排。因此，这样一个工具将加速跨部门和机构已经资助的项目（主要是NIH），并扩大其范围。它还将更好地利用区域设施进行后续改进研究，而不是常规的早期实验。

DESCRIPTION (provided by applicant): A high field multinuclear NMR spectrometer is needed to support new and ongoing projects at Marquette University and the greater Milwaukee area. The proposed instrument will support and extend existing NIH and other funded projects for 6 major users and 4 minor users from 3 institutions. The major user group is funded by 8 NIH grants, and minor users are funded from various sources. The major users are involved in projects directed to problems in biochemistry that make central use of NMR, and the minor users have projects that rely heavily on NMR in a supporting role. A key feature required of the spectrometer will be the high sensitivity and resolution available at 600 MHz, in order to study protein-ligand interactions. The NMR facility will offer a wide variety of probe choices, including MicroFlow and BB, thereby satisfying a regional need unmet by other facilities. Projects include: (1) Probing protein-ligand interactions in chemical proteomics: NMR methods development and application (Sem), (2) Complementary use of NMR and Raman studies to probe ligand binding to cytochrome P450cam (Kincaid), (3) Role of Su e information of the Fi-Fo ATP synthase dimeric complex: structural and binding studies (Stuart), (4) Mechanism of flagellar radial spoke: ligand binding and structural studies of radial spoke protein 2 (RSP2) (Yang), (5) Structural characterization of molecular motions in NADPH-dependant cytochrome P450 oxidoreductase (Kim) and (6) Substrate binding geometries in Fell dependent non-heme oxygenases from paramagnetic relaxation and heteronudear correlation (Moran). The spectrometer is the center-piece of the "Chemical Proteomics Facility at Marquette", and accordingly has the strong support of Marquette University which has committed the additional $368,945 needed beyond the $500,000 being requested, as well as needed space, facilities, staff, cryogens, warranties and other support. Although neighboring NMR facilities are currently being used, they cannot meet existing demand due largely to the need for travel of > 100 miles and advance scheduling for routine high-field experiments. Such an instrument would therefore accelerate already funded (predominantly NIH) projects across departments and institutions, as well as extend their scope. It will also better leverage the use of regional facilities for follow-up refinement studies, rather than routine early-stage experiments.