The bio-molecular research community in the Los Angeles area is requesting NIH funding to purchase a state-of-art pulse electron paramagnetic resonance (EPR) spectrometer, the EleXsys FT-EPR system from Bruker Corporation. Pulse EPR spectroscopy is a powerful tool for analyzing conformations and metal ion cofactors of biological systems. The proposed pulse EPR spectrometer simultaneously will provide two capabilities that are central to the participating users. One is Double Electron Electron Resonance (DEER) spectroscopy, which selectively measures electron spin dipolar interactions to yield inter-spin distances up to 80 ? in bio-molecules. The measured distances provide direct structural constraints for mapping global structures and monitoring conformational changes of complex bio-molecular systems. User projects that require DEER span many important public health related areas, including viral replication and infection (X. Chen, Goodman, Qin), protein trafficking (Shan), transcription regulation (L. Chen), and human chromosomal translocation (Lieber). The second type of pulse EPR measurement is Electron Nuclear Double Resonance (ENDOR) and Electron Spin Echo Envelope Modulation (ESEEM), which measure interactions between the electron spin and the surrounding nuclei. This will be used to study ligand identity and coordination geometry of metal co-factors in nitrogenase (Rees, McKenna), DNA polymerase (McKenna, Crans, Goodman), and amoyloid formation in Alzheimer's disease (Zhou). Pulse EPR capabilities are grossly inadequate at the participating institutions. Funding of the proposed instrument will significantly benefit on-going research in the group of users, which are currently supported by 23 NIH grants. It will also support the broader regional research community, training of minorities, and educational missions. The award will immediately impact approximately 500 jobs in American, thus stimulating the economy.
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