Download Solution Structure of the Cell Adhesion Matrix Protein,Syndecan

High Resolution NMR Application to Biological Science: Structure,
Function and Drug Design
Weontae Lee
Department of Biochemistry , College of Life Science & Biotechnology
Yonsei University, Seoul, Korea
High-resolution NMR technique has been used as one of the powerful techniques to
study biochemical problems. In this talk, heteronuclear multi-dimensional NMR
application of three different biological systems will be presented. (1) The
comprehensive view of both human and other model organisms has been given by
enormous success of genome projects. The wealth of sequence information provided an
important initiative for structural biologists to extract structure-function of proteins.
NMR based Structural proteomics will be a challenging research area, supplying tens of
thousands protein structures in a short period of time. This will promise us the predicted
biological functions to a large number of new proteins, which is so call structure-based
function discovery. (2) Syndecans, transmembrane heparan sulfate proteoglycans, are
coreceptors with integrin in cell adhesion. It has been suggested to form a ternary
signaling complex with protein kinase C and its ligand, PIP2. The solution
conformations of syndecan and ligand bound form have been determined by
heteronuclear NMR spectroscopy. Our results shows that PIP2 promotes
oligomerization of syndecan-4 cytoplasmic domain for transmembrane cell adhesion
signaling and variable region of 4L plays an important function in this signaling
procedures. (3). Naturally occuring bioactive peptides and small proteins that regulate
their relevant biological activities have been considered as strong candidates for rational
drug designs. High resolution NMR would be a powerful tool to analyze structurefunctuon of small peptides for structure-based drug design (SBDD). Melanocytestimulating hormone (MSH) and melanocortin receptors are the key components of the
hypothalamic response to obesity. The solution structures of MSH and peptidomimetic
analogs have been determined by two- dimensional NMR spectroscopy and simulatedannealing calculations. We could evaluate the effects of the size and electronic changes
of the residues neighboring the message sequence on the selectiveness to the receptors
from receptor-ligand complex structures. Therefore, NMR together with functional
information will serve as an excellent technique for structure-based drug design for
obesity control.