Acquisition of an 800MHz Nuclear Magnetic Resonance Spectrometer for Structural Biology

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The research to be conducted on the new instrument funded by this award relates to solution structural studies on biomolecules using nuclear magnetic resonance (NMR) spectroscopy. It will be directed at aspects of protein structure and dynamics in solution and will involve determination of structures of medium to large proteins, both alone and in complex with small peptides, DNA oligonucleotides or other proteins, and will include examination of dynamics of regions important for recognition of other proteins or DNA. These studies are of a basic nature and will provide mechanistic understanding of processes of ligand recognition and mode of action. Four principal research groups at the University of Illinois at Chicago and an investigator in the chemistry department at nearby Loyola University of Chicago will be the major users of the instrument. Projects include (i) understanding the specificity of binding of the multiple protein ligands of the broad specificity clearance receptor LRP that is involved in metabolism of proteases and lipoproteins, (ii) understanding the molecular basis for recognition of regulatory DNA sequences by a transcription factor protein family, (iii) determination of the structure of domains from the erythrocyte skeletal protein spectrin that are responsible for the shape and flexibility of red blood cells (iv) examination of the mechanism of infection of cells by HIV. The award will be used to purchase a state-of-the art narrow bore 800MHz NMR spectrometer fully equipped for multinuclear, multidimensional, gradient enhanced solution structural studies on bio-macromolecules. The instrument will be housed in custom-designed space. This instrument will complement an existing 600MHz NMR spectrometer that is currently available on campus for determination of protein solution structures, but that lacks the capabilities of the higher field instrument for tackling the very challenging problems described. The 800MHz NMR spectrometer and the studies to be carried out on it will be of great benefit both for improving the research infrastructure of the university and of the Chicago structural biology community and for enhancing the training opportunities for the area students. State-of-the-art highest field NMR instrumentation, as represented by the awarded equipment, will be unique in metropolitan Chicago and will permit the continued development of already active NMR programs into the more challenging, but also most exciting and rewarding areas. This will contribute significantly to the competitiveness of these research programs, their success and hence visibility, which in turn will help both in recruitment of additional structurally-oriented faculty, postdocs and students and in fostering collaborations between faculty within the university and Chicago. All of the investigators currently train both graduate students and postdocs and so offer training opportunities in use of NMR to examine protein structure; an area that is already of the most fundamental importance to all biological sciences, and that will continue to grow in the post-genomic era. The acquisition of an 800MHz spectrometer will enable such students to work and train on the most challenging projects and so acquire skills that will be needed for careers in the critical biotechnology, pharmaceutical, and molecular medicine industries.