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Barbara Brodsky
Professor
UMDNJ
Dept. Biochemistry - Room 609
Piscataway. NJ 08854
(732) 235-4048
FAX - 4783
brodsky@umdnj.edu |
Structural studies of peptide models of
normal collagen and its mutations in diseases
The aims of our laboratory are to use
triple-helical peptides of defined sequence to determine how amino acid sequence
affects triple-helix structure and recognition. and how alterations in the
triple-helix can lead to molecular defects in collagen diseases. Triple-helical
domains are important both as a rod-like structural component and for
interactions with other molecules in collagens and in a range of host-defense
proteins. Synthetic triple-helical peptides have been designed to model
biologically important regions of collagen and of the macrophage scavenger
receptor. The conformation. stability. dynamics. folding and binding of these
peptides are being characterized through the use of circular dichroism
spectroscopy. calorimetry. NMR spectroscopy. molecular modeling. and x-ray
crystallography. Mutations that interrupt the repeating (Gly-X-Y)n have been
found to lead to connective tissue diseases. and studies are being done to
investigate the structural basis of these pathological changes. Recent
accomplishments include determination of the first crystal structures of a
triple-helix. in collaboration with the laboratory of Dr. Helen Berman; the
first 2-D NMR structural and dynamics studies on a triple-helix. in
collaboration with Dr. Jean Baum; establishment of propensities scales for the
collagen triple-helix; and determining the degree of destabilization caused by
different Gly mutations in collagen diseases.
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