We propose to purchase a 750 MHz multi-nuclear high-resolution NMR system primarily for use of the University of Michigan Chemistry/Biological Chemistry NMR community. The instrument will be used for experiments leading to the determination of high-resolution three-dimensional structures and dynamics of proteins, nucleic acids and their complexes, in the molecular weight range 20-30 kDa, in solution. The major virtue of the new instrument is an improvement of at least a factor of two in sensitivity as compared to currently accessible instruments, bringing the structural studies of these more difficult and more abundant systems within reach. Projects benefitting from this acquisition are: structural studies of the molecular chaperone proteins Hsc-70 and DnaK, structural studies of Stromelysin and its complexes with inhibitors and substrate, structural studies of proteins expressed by the E. coli Ars-Operon, structural elucidation of Cytidylyltransferase, design of Cysteine Protease Inhibitors, synthesis of improved DNA binding carbohydrates, dynamics of DNA triple helices, elucidation of anti-DNA autoantibodies antigen interaction, structure of soluble and of membrane-spanning domains of the GABAA receptor.
