Multifrequency Pulsed Electron Paramagnetic Resonance Spectrometer For Biomedical

生物医学用多频脉冲电子顺磁共振波谱仪

• 批准号: 7590971
• 负责人: SERGEI A DIKANOV
• 金额: $ 39.71万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7590971
• 关键词: Academia; Am 580; Arts; Binding; Biological Sciences; Biomedical Research; Catalysis; Catalytic Domain; Communities; Dependence; Development; Drug Design; Electron Spin Resonance Spectroscopy; Environment; Enzymes; Frequencies; Funding; Genome; Illinois; Industry; Investigation; Ions; Kinetics; Knowledge; Magnetism; Measures; Medical; Metal Binding Site; Molecular; Molecular Biology; Molecular and Cellular Biology; Names; Nuclear; Nucleotides; Oxidation-Reduction; Physiologic pulse; Proteins; Relaxation; Request for Proposals; Research; Research Project Grants; Schools; Science; Site; Solvents; Structure; Surveys; System; instrument; public health relevance; research facility; structural biology; tool

DESCRIPTION (provided by applicant): This proposal requests addition of S-band (3.5 GHz) and Q-band (35 GHz) capability to the X-band (9.5 GHz) pulsed Electron Paramagnetic Resonance (EPR) spectrometer system (ELEXSYS, E-580) currently available on campus. This will provide a strong and diverse biomedical research community on this campus, and external users from academia and industry, with a versatile, state-of-the art tool in EPR spectroscopy for structural biology. The proposed enhancement is particularly critical for the successful development of research projects performed by six named NIH-funded major-user groups. The instrument will be sited in UIUC EPR Research facility space within the School of Molecular and Cellular Biology (SMCB), and will be operated and managed under the SMCB administrative umbrella. The ELEXSYS E- 580 was previously under management by the Illinois EPR Research Center, and that unit was reorganized within SMCB subsequent to the reorganization of the life sciences on campus. PUBLIC HEALTH RELEVANCE: A main focus of modern molecular biology is on understanding how structure at the molecular level defines mechanism and function. This interface is of critical importance in understanding catalysis, effector binding, drug design, etc., indeed the whole underpinning of the medical sciences by molecular biology. Surveys suggest that >30% of the protein-encoding genome encodes either redox proteins, or proteins that include metal binding sites suitable for probing by EPR. Pulsed EPR approaches follow the relaxation kinetics of paramagnetic centers and the modulation by interaction with nuclear magnetic centers in the protein and solvent. By Fourier transformation, the frequencies of the nuclear magnets, and hence their atomic identities, distance and angles, can be measured. The distance dependence of the interaction selects that volume most closely associated with the catalytic domain. Redox enzymes generate paramagnetic centers naturally, while, for example, nucleotide binding enzymes where the Mg2+chelate is the substrate can be probed by replacing the ion by paramagnetic substituents. For these paramagnetic systems, pulsed EPR is an ideal approach for investigation of the protein environment immediately adjacent to the functional center, and is therefore an invaluable tool in the advancement of medical knowledge.

描述（由申请人提供）：本提案要求将S波段（3.5 GHz）和Q波段（35 GHz）能力添加到校园内目前可用的X波段（9.5 GHz）脉冲电子顺磁共振（EPR）光谱仪系统（ELEXERAND，E-580）。这将在这个校园里提供一个强大而多样化的生物医学研究社区，以及来自学术界和工业界的外部用户，为结构生物学提供EPR光谱学方面的多功能，最先进的工具。拟议的增强功能对于六个指定的NIH资助的主要用户团体执行的研究项目的成功开发尤其重要。该仪器将位于分子和细胞生物学学院（SMCB）内的UIUC EPR研究设施空间，并将在SMCB行政保护伞下运行和管理。ELEXTREE- 580以前由伊利诺伊州EPR研究中心管理，该单位在校园生命科学重组后在SMCB内重组。公共卫生相关性：现代分子生物学的一个主要焦点是了解分子水平的结构如何定义机制和功能。这种界面在理解催化、效应物结合、药物设计等方面至关重要，事实上，整个医学的基础都是分子生物学。调查表明，>30%的蛋白质编码基因组编码氧化还原蛋白，或包含适合EPR探测的金属结合位点的蛋白质。脉冲EPR方法遵循顺磁中心的弛豫动力学以及通过与蛋白质和溶剂中的核磁中心相互作用的调制。通过傅里叶变换，可以测量核磁体的频率，从而测量它们的原子身份、距离和角度。相互作用的距离依赖性选择与催化域最密切相关的体积。氧化还原酶天然地产生顺磁性中心，而例如，其中Mg 2+螯合物是底物的核苷酸结合酶可以通过用顺磁性取代基替换离子来探测。对于这些顺磁系统，脉冲EPR是一种理想的方法，用于研究紧邻功能中心的蛋白质环境，因此是医学知识进步的宝贵工具。