Multifrequency Pulsed Electron Paramagnetic Resonance Spectrometer For Biomedical

描述（由申请人提供）：该提案要求在校园现有的x波段（9.5 GHz）脉冲电子顺磁共振（EPR）光谱仪系统（ELEXSYS, E-580）的基础上增加s波段（3.5 GHz）和q波段（35 GHz）能力。这将为这个校园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，为结构生物学提供一个多功能的，最先进的EPR光谱工具。拟议的改进对于由六个指定的nih资助的主要用户组执行的研究项目的成功发展尤为关键。该仪器将位于UIUC分子和细胞生物学学院（SMCB）内的EPR研究设施空间，并将在SMCB行政保护伞下运行和管理。ELEXSYS E- 580之前由伊利诺斯州EPR研究中心管理，随着校园生命科学的重组，该部门在SMCB内进行了重组。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上的结构如何定义机制和功能。这个界面对于理解催化、效应结合、药物设计等至关重要，实际上是整个分子生物学医学科学的基础。研究表明，大约30%的蛋白质编码基因组编码氧化还原蛋白或含有适合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，可以测量核磁铁的频率，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了与催化结构域最密切相关的体积。氧化还原酶自然产生顺磁性中心，而例如，以Mg2+螯合物为底物的核苷酸结合酶可以通过顺磁性取代基取代离子来探测。对于这些顺磁系统，脉冲EPR是研究紧邻功能中心的蛋白质环境的理想方法，因此是医学知识进步的宝贵工具。

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.