USE OF F-19 NMR TO PROBE PROTEIN-STRUCTURE AND CONFORMATIONAL-CHANGES

F-19 NMR has proven to be a powerful technique in the study of protein structure and dynamics because the F-19 nucleus is easily incorporate d at specific labeling sites, where it provides a relatively nonpertur bing yet sensitive probe with no background signals. Recent applicatio ns of F-19 NMR in mapping out structural and functional features of pr oteins, including the galactose-binding protein, the transmembrane asp artate receptor, the CheY protein, dihydrofolate reductase, elongation factor-Tu, and D-lactose dehydrogenase, illustrate the utility of F-1 9 NMR in the analysis of protein conformational states even in molecul es too large or unstable for full NMR structure determination. These s tudies rely on the fact that the chemical shift of F-19 is extremely s ensitive to changes in the local conformational environment, including van der Waals packing interactions and local electrostatic fields. Ad ditional information is provided by solvent-induced isotope shifts or line broadening of the F-19 resonance by aqueous and membrane-bound pa ramagnetic probes, which may reveal the proximity of a F-19 label to b ulk solvent or a biological membrane. Finally, the effect of exchangin g conformations on the F-19 resonance can directly determine the kinet ic parameters of the conformational transition.