Title: Associate Professor, Bioinorganic Chemistry
Office: SZ 561
Phone: (252) 328-9796
Postdoctoral research, Dartmouth College (2003-2007)
Ph.D., Chemistry, Yale University (2003)
BS, Chemistry, Syracuse University (1996)
General Chemistry I (CHEM 1150)
General Chemistry Lab I (CHEM 1151)
Elemental Inorganic Chemistry (CHEM 3450)
Inorganic Chemistry Lab (CHEM 3451)
Advanced Inorganic Chemistry (CHEM 5550)
General Chemistry Lecture Coordinator Fall 2009 to Spring 2011
Guest Lecturer Brody School of Medicine Physical Biochemistry Spring 2009
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 the 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.
R. A. Johnson, O. M. Manley, A. M. Spuches, N. E. Grossoehme. Dissecting ITC data of metal ions binding to ligands and proteins. Biochimica et Biophysica Acta. 1860(5), 892-901, 2016.
D. P. Gogineni, A. M. Spuches, C. S. Burns. Calorimetric Investigation of Copper Binding in the N-Terminal Region of the Prion Protein at Low Copper Loading: Evidence for an Entropically Favorable First Binding Event. Inorganic Chemistry, 54(2), 441-447, 2015.
R. A. Skowronsky, M. Schroeter, T. Baxley, Y. Li, J. M. Chalovich, A. M. Spuches. Thermodynamics of Calcium Binding to the Regulatory Site of Human Cardiac TnC: Evidence for Communication with the Structural Calcium Binding Sites. Journal of Biological Inorganic Chemistry. 18(1), 49-58, 2013.
C. Sacco, R. A. Skowronsky, S. Gade, J. M. Kenney, A. M. Spuches. Calorimetric Investigation of Copper (II) Binding to Aβ Peptides: Thermodynamics of Coordination Plasticity. Journal of Biological Inorganic Chemistry. 17 (4), 531-541, 2012.
A. L. Russell, A. M. Spuches, B.C. Williams, D. Venugopal, D. Klapper, A. H. Srouji, and R. P. Hicks. The Effect of the Placement and Total Charge of the Basic Amino Acid Clusters on Antibacterial Organism Selectivity and Potency. Bioorganic and Medicinal Chemistry. 19, 7008-7022, 2011.
A. L. Russell, A. M. Kennedy, A. M. Spuches, W. S. Gibson, D. Venugopal, D. Klapper, A. H. Srouji, J.B. Bhonsle and R. P. Hicks. Determining the Effect of the Incorporation of Unnatural Amino Acids into Antimicrobial Peptides on the Interactions with Zwitterionic and Anionic Membrane Model Systems. Chemistry and Physics of Lipids, 164, 740-758, 2011.
S. Siamakpour-Reihani, A. M Bradford, T. A. Peterson, H. J. Argiros, L. L. Haas, S.N. Lor, Z. M. Haulsee, A. M. Spuches, D. L. Johnson, L. R. Rohrschneider, C. B. Shuster and B. A. Lyons. Grb7 Binds to Hax-1 and Undergoes an Intramolecular Domain Association that Offers a Model for Grb7 Regulation. Journal of Molecular Recognition, 24 (2), 314-321, 2011
A. L. Russell, A. M. Kennedy, A. M. Spuches, D. Venugopal and R. P. Hicks. Spectroscopic and Thermodynamic Evidence for Antimicrobial Peptide Membrane Selectivity. Chemistry and Physics of Lipids. 163, 488-497, 2010.
N. E. Grossoehme, A. M. Spuches, D. E. Wilcox. Application of isothermal titration calorimetry in bioinorganic chemistry. Journal of Biological Inorganic Chemistry. 15 (8), 1183-1191, 2010.
J. V. Gavette, J. M. McGrath, A. M. Spuches, A. L. Sargent and W. E. Allen. Fluorous Effects in Amide-Based Receptors for Anions. Journal of Organic Chemistry. 74 (10), 3706-3710, 2009.
A. M. Spuches and D. E. Wilcox. Monomethylarsenite Competes with Zn2+ for Binding Sites in the Glucocorticoid Receptor. Journal of the American Chemical Society, 130 (26): 8148-8149, 2008.
A. M. Spuches, H. J. Argiros, K. H. Lee, L. Lowell Haas, S.C. Pero, D. N. Krag, P. P. Roller, D. E. Wilcox and B. A. Lyons. Calorimetric Investigation of Phosphorylated and non-Phosphorylated Peptide Ligand Binding to the Human Grb7-SH2 Domain. Journal of Molecular Recognition, 20 (4): 245-252, 2007.
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.
M. Chung, X.Gu, B. A. Etzenhouser, A. M. Spuches, P. T. Rye, S. K. Seetharaman, D. Rose, J. Zubieta, M. B. Sponsler. Intermetal Coupling in [(η5-C5R5)Fe(dppe)]2M (µ-CH=CHCH=CH) and in their Dicationic and Monocationic Mixed-valence Forms. Organometallics. 22 (17): 3485-3494, 2003.