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.
Ongoing Research Interests
Selected Publications
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.
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