600 MHz Nuclear Magnetic Resonance Spectrometer

描述(由申请人提供)：马奎特大学和大密尔沃基地区需要一台高场多核核磁共振光谱仪来支持新的和正在进行的项目。拟议的文书将支持和扩大现有的国家卫生研究院和其他资助项目，供3个机构的6个主要用户和4个次要用户使用。主要用户群体由NIH的8笔赠款资助，而次要用户则从各种来源获得资助。主要用户参与针对生物化学问题的项目，集中使用核磁共振，而次要用户的项目在很大程度上依赖于核磁共振的辅助作用。为了研究蛋白质-配体的相互作用，光谱仪的一个关键特征是在600 MHz处具有高灵敏度和高分辨率。核磁共振设施将提供多种探头选择，包括微流和BB，从而满足其他设施无法满足的地区需求。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：核磁共振方法的发展和应用(Sem)，(2)补充使用核磁共振和拉曼研究来探测与细胞色素P450 cam(Kincaid)结合的配体，(3)Fi-Fo ATP合成酶二聚体复合体的SU e信息的作用：结构和结合研究(Stuart)，(4)鞭毛径向辐射的机制：径向辐射蛋白2(RSP2)的配体结合和结构研究(Yang)，(5)NADPH依赖的细胞色素P450氧化还原酶(KIM)中分子运动的结构特征和(6)Fell依赖的非血红素加氧酶中底物结合几何构型的顺磁驰豫和杂链相关(Moran)。光谱仪是“马奎特化学蛋白质组学设施”的核心部分，因此得到了马奎特大学的大力支持，该大学承诺在所要求的500,000美元之外再提供368,945美元，以及所需的空间、设施、工作人员、冰箱、保修和其他支持。尽管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，主要是因为需要旅行100英里，以及提前安排常规高场实验的时间。因此，这样一项文书将加快各部门和机构之间已经得到资助(主要是国家卫生研究院)的项目，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，而不是常规的早期试验。

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.