800 MHZ SPECTROMETER FOR BIOMOLECULAR NMR: EAR RESEARCH, DEAFNESS

用于生物分子 NMR 的 800 MHZ 光谱仪：耳朵研究、耳聋

• 批准号: 7335093
• 负责人: Steven R Van Doren
• 金额: $ 5.5万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2007-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7335093
• 关键词: DNA; ear; ligands; neoplasm /cancer; proteins; university; urban area; zinc

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): Seven groups of NMR users from the Columbia, St. Louis, and Kansas City campuses of the University of Missouri and from Washington University-St. Louis seek the first 800 MHz NMR spectrometer for the state of Missouri. The high field spectrometer will introduce structural biology of greater significance to their NIH projects. The University of Missouri-Columbia (UMC), in the geographical center of the life sciences corridor from St. Louis through Kansas City, will host the 800 MHz system. The advisory committee for deciding policy for the 800 will have broad representation from St. Louis to Kansas City. A fee system, uniformly applied among all users, will recover most of the operating costs of the 800. UMC offers a large matching package and new space tailored to hosting the 800 within a new building of its School of Medicine. The funds requested will be applied to an 800 MHz spectrometer with a shielded 18.8 T magnet. A cryogenic probe for outstanding sensitivity remains an additional high priority. The boosts in sensitivity, resolution, and TROSY line sharpening afforded by 800 MHz are needed by all these groups now using 600 MHz equipment. Four groups will employ the 800 for cancer-related work. The Van Doren group will investigate (i) interactions of metalloproteases with inhibitor and substrate proteins and (ii) interactions of transforming tumor viral proteins with their target proteins of host cells. Ma and Deutscher will determine NMR structures of galectin-3 bound to a tumor-targeting peptide and a full-length galectin-3 dimer. Ellen Li's group will investigate how ligands shift the equilibrium dynamics of retinoid-X-receptor (RXR) ligand binding domain. John-Stephen Taylor's group will obtain more detailed structural insights on DNA photoproducts underlying skin cancer. Henzl will study structural features and interactions of principal proteins (OCP2 and OCP1) in the auditory organ of the inner ear, a complex that binds connexin 26 most often mutated in hereditary deafness. Three groups will study DNA-binding protein assemblies. Dupureur's group will undertake the first NMR investigations of dynamics and conformational adjustments of a restriction endonuclease in response to DNA binding and conditions of "star activity". Laity will study structure and dynamics of the zinc-sensing DNA-binding domain of metal-responsive transcription factor-1 that regulates zinc homeostasis in mammals. He will study all six of its zinc fingers free and bound to DNA. Dreyfus and Laity will characterize the structure and dynamics of cytolethal CdtB toxin from pathogenic bacteria, free and bound to DNA. The CdtB subunit is sufficient to cause DNA damage and to arrest the cell cycle in mammalian cells.

该副本是利用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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是赠款，这不一定是调查人员的机构。描述（由申请人提供）：来自哥伦比亚，圣路易斯和密苏里大学堪萨斯城校园的七个NMR用户和华盛顿大学。路易（Louis）寻求密苏里州的第一个800 MHz NMR光谱仪。高场光谱仪将引入其NIH项目具有更大意义的结构生物学。密苏里大学哥伦比亚大学（UMC）位于圣路易斯到堪萨斯城的生命科学走廊地理中心，将拥有800 MHz系统。决定800的政策咨询委员会将从圣路易斯到堪萨斯城的广泛代表。所有用户中均匀应用的费用系统将收回800的大部分运营成本。UMC提供了一个大型匹配的包装和新的空间，该套件是为在其医学院的新建筑物中托管800的新空间。所需的资金将应用于带有18.8 T磁铁的800 MHz光谱仪。对出色灵敏度的低温探针仍然是额外的高优先级。现在，所有这些组都使用600 MHz设备，所有这些组都需要800 MHz提供的敏感性，分辨率和Trosy线的提升。四组将雇用800人进行与癌症有关的工作。 Van Doren组将研究金属蛋白酶与抑制剂和底物蛋白的相互作用，以及（ii）转化的肿瘤病毒蛋白与宿主细胞的靶蛋白的相互作用。 MA和Deutscher将确定结合靶向肿瘤的肽和全长Galectin-3二聚体结合的半乳糖素3的NMR结构。艾伦·李（Ellen Li）的组将研究配体如何改变类维生素类-X受体（RXR）配体结合域的平衡动力学。约翰·斯蒂芬·泰勒（John-Stephen Taylor）的小组将获得有关皮肤癌潜在的DNA光产物的更详细的结构见解。 HENZL将研究内耳听觉器官中主蛋白（OCP2和OCP1）的结构特征和相互作用，这种复合体结合了连接性的26最常在遗传性耳聋中突变。三组将研究DNA结合蛋白组件。杜普雷尔（Dupureur）的小组将对限制性核酸内切酶的动力学和构象调整进行首次NMR研究，以响应DNA结合和“恒星活性”的条件。 Laity将研究金属响应转录因子1的锌感应DNA结合结构域的结构和动力学，从而调节哺乳动物的锌稳态。他将免费研究其所有六个锌手指并与DNA结合。 Dreyfus和Laity将表征来自病原细菌的细胞杀伤CDTB毒素的结构和动力学，自由并与DNA结合。 CDTB亚基足以引起DNA损伤并阻止哺乳动物细胞中的细胞周期。