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David Jones, Associate Professor

Ph.D.(1990), University of Cambridge, UK
 

 

 

Contact Info:

Molecular Biology
University of Colorado

David Jones, Ph.D.  Research One South
(RC1-South), Room 6116 David.Jones@ucdenver.edu Phone: 303-724-3600

The use of NMR Spectroscopy to Probe the Relationship Between Protein Structure and Disease

I am interested in understanding how the three-dimensional structure of proteins and nucleic acids controls their biological function. Changes in the chemical composition of a protein, perhaps through a spontaneous mutation can disrupt its structure which may dramatically interfere with its normal function. This in turn can lead to the development of diseases such as cancer. Understanding the fine balance between structure and function and how these correlate with the onset of disease is one of the major challenges for pharmacologists and biochemists today. If we can find out how the structure of a molecule defines its biological function we can begin to design new pharmaceutical drugs for fighting disease.

Research in my lab uses Nuclear Magnetic Resonance (NMR) spectroscopy to study the structure and dynmaics of biological molecules implicated in the development and progression of disease.

NMR spectroscopy is used to solve the three dimensional structures of molecules in solution. However this is only the first step in understanding structure-function relationships in proteins. NMR is one of the only techniques that can provide information about how flexibility of a protein contributes to its function. As an example, many proteins change their structure on binding to a drug or other ligand. Understanding the dynamics was an important part of the design of HIV protease inhibitors for the treatment of AIDS patients. My laboratory uses NMR to probe the contributions that dynmaic processes make to understanding the function of proteins.

 

A strip-plot showing the NMR assignments for a region of a protein involved in activation of a G-protein coupled receptor.

 

Jones, D.N.M. and Bendiak, B., Novel Heteronuclear NMR Methods for the study of C13-O-Acetylated Oligosaccharides: Extending the Dimensions for Carbohydrates. J. Biomol. NMR, (1999), 15: p. 157-168.

Wang, B., Jones, D.N.M., Kaine, B.P., and Weiss, M.A., High-resolution structure of an archaeal zinc ribbon defines a general architectural motif in eukaryotic RNA polymerases. Structure, (1998), 6(5): p. 555-569.

Burkoth, T.S., Benzinger, T.L.S., Jones, D.N.M., Hallenga, K., Meredith, S.C., and Lynn, D.G., C-terminal PEG blocks the irreversible step in beta-amyloid(10- 35) fibrillogenesis. J. Amer. Chem. Soc., (1998), 120(30): p. 7655-7656.

Benzinger, T.L.S., Braddock, D.T., Dominguez, S.R., Burkoth, T.S., Miller-Auer, H., Subramanian, R.M., Fless, G.M., Jones, D.N.M., Lynn, D.G., and Meredith, S.C., Structure-function relationships in side chain lactam cross- linked peptide models of a conserved N-terminal domain of apolipoprotein E. Biochemistry, (1998), 37(38): p. 13222-13229.

Fletcher, C.M., Jones, D.N.M., Diamond, R., and Neuhaus, D., Treatment of NOE constraints involving equivalent or nonstereoassigned protons in calculations of biomacromolecular structures. J. Biomol. NMR, (1996), 8(3): p. 292-310.

Churchill, M.E.A., Jones, D.N.M., Glaser, T., Hefner, H., Searles, M.A., and Travers, A.A., HMG-D Is an Architecture-Specific Protein That Preferentially Binds to DNA Containing the Dinucleotide TG. EMBO Journal, (1995), 14(6): p. 1264-1275.

Jones, D.N.M., Searles, M.A., Shaw, G.L., Churchill, M.E.A., Ner, S.S., Keeler, J., Travers, A.A., and Neuhaus, D., The Solution Structure and Dynamics of the DNA-Binding Domain of HMG-D From Drosophila melanogaster. Structure, (1994), 2(7): p. 609-627.

For more information, please visit Ongoing Research Interests.