Anne M. Spuches

Professor,
Bioinorganic Chemistry

  • Postdoctoral research, Dartmouth College (2003-2007)
  • Ph.D., Chemistry, Yale University (2003)
  • BS, Chemistry, Syracuse University (1996)

Research Overview

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.

Selected Publications

  • Roberts DE, Benton AM, Fabian-Bayola C, Spuches AM, Offenbacher AR. Thermodynamic and Biophysical Study of Fatty Acid Effector Binding to Soybean Lipoxygenase: Implications for Allostery Driven by Helix α2 Dynamics. FEBS Letters, 596, 350–359, 2022.
  • Rayani K, Seffernick J, Li AY, Davis JP, Spuches AM, Van Petegem F, Solaro RJ, Lindert S, Tibbits GF. Binding of calcium and magnesium to human cardiac Troponin C. Journal of Biological Chemistry, 296, 100350, 2021.
  • Banerjee S, Garrigues RJ, Chanakira MN, Negron-Olivero JJ, Odeh YH, Spuches AM, Roop MR, Pitzer JE, Martin, DW, Dasgupta S. Investigating the roles of the conserved Cu(II)-binding residues on Brucella FtrA in producing conformational stability and functionality. Journal of Inorganic Biochemistry, 210, 111162, 2020.
  • A. Johnson, L. M. Fulcher, K. Vang, C. D. Palmer, N. E. Grossoehme, and A. M. Spuches. In depth, Thermodynamic Analysis of Ca2+ Binding to Human Cardiac Troponin C: Extracting Buffer-independent Binding Parameters. Biochimica Biophysica Acta-Proteins and Proteomics, 1867, 359–366, 2019.
  • A. Johnson, O. M. Manley, A. M. Spuches, N. E. Grossoehme. Dissecting ITC Data of Metal Ions Binding to Ligands and Proteins. Biochimica Biophysica Acta-General Subjects, 1860 (5), 892-901, 2016.
  • P. Gogineni, A. M. Spuches, and 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.