Anne M. Spuches
Assistant Professor, Inorganic Chemistry
- Postdoctoral research, Dartmouth College (2003-2007)
- Ph.D., Chemistry, Yale University (2003)
- BS, Chemistry, Syracuse University (1996)
Research in Dr. Spuches’s lab focuses on how metals (both toxic and essential) are “trafficked” within the cell. Metals play many important roles in biochemistry and all organisms require metal ions to carry out very specific functions. However, many of the essential metals such as copper and iron are redox active and unless tightly regulated are highly toxic. Our goal is to understand how metals are regulated within the intra-cellular milieu. To achieve this understanding, we use thermodynamic and spectroscopic techniques to characterize the thermodynamics and kinetics of metals binding to various biological molecules such as peptides, proteins, and enzymes. Once we have this information in hand, we can begin to build models that describe the distribution of metal ions in the cell.
An important technique used in the laboratory is isothermal titration calorimetry (ITC). ITC measures the heat released or absorbed during a reaction or binding event. In a single titration experiment, one obtains three key pieces of information regarding metal binding: binding constants (K), enthalpies (∆H), and stoichiometries (N). With this information one can calculate Gibbs free energy of binding (∆G), and the entropy (∆S) of the system thus providing a full thermodynamic survey of metal binding to the molecule This information is important for understanding how tightly metal ions are associated to biological molecules and provides insight into what factors contribute to this interaction.
Selected Publications:
A. M. Spuches, A. M. Rich, A. D. Schenk, B. Rouse, H. A. Godwin, D. E. Wilcox. Thermodynamics of Zinc and Cobalt Binding to the DNA Binding Domain of Glucocorticoid Receptor. Manuscript in Preparation.
A. M. Spuches, J. E. Bodwell, J. W. Hamilton, and D. E. Wilcox. A Thermodynamic Analysis of Arsenite and Monomethylarsenite Interactions with the Glucocorticoid Receptor. Manuscript in Preparation.
A. M. Spuches, H. J. Argiros, K. H. Lee, L. Lowell Haas, S. C. Pero, D. N. Krag, P. P. Roller, D. E. Wilcox, B., A. Lyons. Calorimetric Investigation of Phosphorylated and Non-Phosphorylated Peptide Ligand Binding to the Human Grb7-SH2 Domain. Journal of Molecular Recognition, Manuscript Submitted.
A. M. Spuches, H.G. Kruszyna, A. M. Rich, and D. E. Wilcox. Thermodynamics of As(III)-Thiol Interaction: Arsenite and Monomethylarsenite Complexes with Glutathione, Dihydrolipoic Acid and Other Thiol Ligands. Inorganic Chemistry, 44 (8): 2964-2972, 2005.
M. Ivancic, A. M. Spuches, E. Guth, M. Daugherty, D. E. Wilcox and B. A. Lyons. Backbone Nuclear Relaxation Characteristics and Calorimetric Investigation of the Human Grb7-SH2/erB2 Peptide Complex. Protein Science, 14 (6):1556-1569, 2005.
