NMR Spectroscopy

Research Interest

We discover three-dimensional structures and structure/function properties of proteins using a combination of multinuclear NMR, biochemistry and X-ray crystallography. We presently concentrate on tumor suppressor proteins that take part in the regulation of the cell-division cycle and in survival genes of tumor cells. Cell division is controlled by series of positive and negative regulators, which act at sequential points throughout the cell division cycle. Disturbances of these checks can lead to uncontrolled cell proliferation and cause cancer. For example, dysregulation of the check proteins of the cell cycle, p53, MDM2, and the retinoblastoma protein account for most human cancers. Potentially our research can lead to developing drugs that retard the cell division of cancer cells. Another group of proteins that we study are actin-binding proteins. Actin and its associated proteins provide basis for the mechanical properties of the cytoskeleton.

Representative Publications

Popowicz, G.M., Schleicher, M., Noegel, A. A. & Holak, T.A. (2006). Filamins: promiscuous organizers of the cytoskeleton. Trends Biochem. Sci. 31, 411-419.

Sitar, T., Popowicz, G.M., Siwanowicz, I., Huber, R. & Holak, T.A. (2006). Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins. Proc. Natl. Acad. Sci. U. S. A. 103, 13028-13033.

Krajewski, M., Ozdowy, P., D’Silva, L., Rothweiler, U. & Holak, T.A. (2005). NMR indicates that the small molecule RITA does not block the p53-MDM2 binding in vitro. Nature Med. 11, 1135-1136.

D'Silva, L., Ozdowy, P., Krajewski, M., Rothweiler, U., Singh, M, & Holak, T.A. (2005). Monitoring the effects of antagonists on protein-protein interactions with NMR spectroscopy. J. Amer. Chem. Soc. 127, 13220-13226.

Muehlhahn, P., Zweckstetter, M., Georgescu, J., Ciosto, C., Renner, C., Lanzendoerfer, M., Lang, K., Ambrosius, D., Baier, M., Kurth, R. & Holak, T.A. (1998). Structure of interleukin 16 resembles a PDZ domain with an occluded peptide-binding site. Nature Struct. Biol. 5, 682-686.

Schnuchel, A., Wiltscheck, R., Czisch, M., Herrler, M., Willimsky G., Graumann, P., Marahiel, M.A. & Holak, T.A. (1993). Structure in solution of the major cold shock protein from Bacillus Subtilis. Nature 364, 169-171.