Our laboratory specializes in nuclear magnetic resonance (NMR)-based structural biology research and is expanding into metabolite profiling applications (metabolomics research). One of our interests is to better understand the molecular links between protein chemical structures, internal dynamics, and biochemical functions. We are interested in answering questions such as: What is the connection between a protein's three-dimensional architecture, flexibility of its amino acids and of its structural elements, and its biological function(s)? How do atomic structures and internal dynamics modulate the biochemical activity of proteins? What is the significance of conserved amino acid residues in protein families?
Our NMR structural biology involves the use of modern multidimensional (1H, 15N, 13C) solution nuclear magnetic resonance (NMR) spectroscopy in conjunction with complementary biophysical techniques. Several proteins are of interest: One consists of an unusual copper(I)-containing protein, NosL, suspected to function as a novel type of copper sensor or metal chaperone.
We have also undertaken cross-disciplinary research with Prof. Andreas Fischer in the Dept. of Plant Sciences to better understand the role of specific proteins in plant senescence and nitrogen mobilization.
Other proteins of interest involve functionally altered variants of the tryptophan repressor protein and understanding the role of protein dynamics in modulating the DNA and co-repressor binding function of these distinct TrpR proteins.
We have also been interested in characterizing proteins derived frome extreme environments such as those originating from organisms living in the hot and acidic thermal pool of Yellowstone National Park. This research is in collaboration with Prof. Martin Lawrence and the Thermal Biology Institute at MSU. Questions of interest focus on: What are the characteristic molecular features of proteins originating from thermophilic organisms that distinguish them from their mesophilic partners? For example, how do thermophilic proteins adapt their structure to function in high temperature and acidic conditions?
Lastly, we have initiated in collaboration with Professor Dratz in the Department of Chemistry and Biochemistry, the development of NMR-based metabolomics research infrastructure to facilitate inter disciplinary research in metabolomics the global study of metabolite concentration, fluxes and regulation. Metabolite levels are closely related to phenotypes and the number of cellular metabolites is much lower than the number of genes or proteins in cells. Metabolic changes are regulated by gene expression and are widely influenced by environmental stresses. We thus anticipate this research will enhance the ability to recognize lead diagnostic markers of cellular responses to pathogen exposure.
Lara Taubner, Ewa Bienkiewicz, Valerie Copiť, and Byron Caughey (2009) Structure of the flexible amino terminal domain of prion protein bound to a sulfated glycan. J. Mol. Biol. in press
A. Goel, B. Tripet, R. Tyler, L. Nebert, J. Carey, and V. Copiť (2009) Part I: Comparison of backbone atom dynamics of the tryptophan repressor protein and functionally altered variants in their apo-
forms. Biochemistry (in prep)
B. Tripet, A. Goel. M. Park, J. Carey, and V. Copiť (2009) Part II: Comparison of backbone atom dynamics of the tryptophan repressor protein and two functionally altered mutants, L75F-TrpR and A77V-TrpR, in their holo forms. Biochemistry (in prep)
Schlenker C., Menon, M., Lawrence, C.M. and V. Copiť (2009) 1H, 13C, 15N Backbone and Sidechain Resonance Assignments for E73 from Sulfolobus Spindle Shaped Virus - Ragged Hills, a Hyperthermophilic Crenarchaeal Virus from Yellowstone National Park. J. Biomol. NMR Assigments. DOI 10.1007/s12104-009-9179-z
V. Copiť (2007) Book Chapter: “Probing the dynamical effects of ligand binding by solution NMR relaxation experiments” In NMR and Drug Screening, Oxford University Press, I. Pelczer, Ed.
Taubner L., McGuirl M., Dooley D., and Copiť V. (2006) Three- dimensional structure of the apo-form of the copper(I) binding protein NosL, originating from the nos gene cluster of Achromobacter Cycloclastes. Biochemistry, Vol. 45, pp. 12240-12252
Hurley, S.P., Clary, D.O., Copiť, V., and Lefcort, F. (2006) Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons and in the peripheral nervous system. J. Comp. Neurobiol., Vol. 495, pp. 202-212
B. L. Moss, L. Taubner, T. K. Sample, D. A. Kazmin, V. Copiť,, and J. R. Starkey (2005) Tumor shedding of the laminin binding protein modulates angiostatin production in vitro and interferes with plasmin-derived inhibition of angiogenesis in aortic ring cultures. Int. J. Cancer, Vol 118, pp 2421-32
M. Jaseja, L. Mergen, K. Gillette, K. Forbes, I. Sehgal,, and V. Copiť (2005) “Structure-function studies of the functional and binding epitope of the human 37 kDa Laminin Receptor Precursor protein” J. Pept. Res. Vol 66, pp. 9-18