Welcome to Professor Prestegard's Home Page

BIOGRAPHICAL SKETCH:

James Prestegard was born in 1944 in Mineapolis MN. He received his B.S. in Chemistry from the University of Minnesota in 1966 and his Ph.D. in Chemistry from Caltech in 1971. He joined the Yale faculty in 1970 where he remained until his move to the University of Georgia in 1998. At Georgia he is director of the Complex Carbohydrate Research Center's (CCRC's) NMR Laboratory, and he is Professor in the Chemistry and the Biochemistry and Molecular Biology Departments. He was recently appointed Eminent Scholar of Nuclear Magnetic Resonance.

RESEARCH INTERESTS:

Interests of the Prestegard group center on the application of Nuclear Magnetic Resonance (NMR) to problems of biological importance. With recent advances in magnet technology and data acquisition methods, NMR spectroscopy is positioned to be an important contributor to understanding the link between macromolecular structure and biological function. NMR has several advantages over more conventional structural methods; it can be applied in a variety of environments, including aqueous solution and membrane phases; it can focus on particularly interesting features, such as the bound ligand of a carbohydrate recognizing protein; and it can provide dynamic, as well as structural, information. At the University of Georgia we have assembled the facilities, including a spectrometer operating at 800 MHz for protons, that are required to both develop new NMR methods and explore their application to forefront problems in biophysical chemistry. Among the problems currently targeted in the lab are those related to how macromolecules function at the surfaces of membranes. Studying interactions at a membrane surface is difficult because the membrane environment is neither crystal nor solution - the two states for which the most effective structure determination methods have evolved. The group has approached this problem by taking advantage of the natural tendency of membrane fragments to form cooperative domains that orient in high magnetic fields. The liquid-crystal- like medium that results, now called a "bicelle" medium, provides moderately high resolution NMR spectra, but retains dipolar splittings of resonances and anisotropic chemical shift offsets that are of proven utility in solids NMR approaches to structure determination. They have been able to use this medium in a number of model systems, one of which is depicted in the figure below.

This system involves the recognition of a cell surface carbohydrate (a glycolipid analog of ganglioside GM3) by a surface active protein (a lectin known for its ability to agglutinate cells). The terminal residue of the glycolipid was enriched with an NMR active isotope, 13C, so that the behavior of this residue could be selectively monitored. Observation of residual dipolar splittings and chemical shift offsets allowed determination of the carbohydrate orientation depicted (green residue). When docked with the binding site of the protein a clear picture of the way in which the protein sits on the surface of the membrane is obtained. The approach involved devising not only a new medium for NMR spectroscopy , but new acquisition methods and new protocols for structural analysis. This is but one example of the work being pursued in the Prestegard group. Please return to our main page for links to other examples.