Through this award, the Chemistry of Life Processes Program is funding Professor Kathryn Splan from Macalester College to study the interaction of copper(I) with zinc finger protein domains. Cu(I) exhibits high affinity for thiolate ligands, which suggests that thiol-rich metalloprotein binding sites such as the ones present in zinc finger domains, may be disrupted at elevated copper concentrations. Professor Splan uses spectroscopic methods to measure the thermodynamic stability- and speciation of- copper-zinc finger peptide complexes. The research tests the ability of Cu(I) to affect the interactions between zinc fingers and DNA, and thus to modulate the function of zinc fingers. The results of this research may be relevant for understanding the mechanism of copper toxicity and homeostasis.
The function of metalloproteins is linked to the metal ion(s) endogenous to the protein. Substitution of the endogenous metals with exogenous ones is likely to alter the structure and function of the protein. The research conducted by Professor Splan and undergraduate students at Macalaster College addresses such a substitution of zinc by copper in a zinc finger protein, which may underline the toxic effect of copper. In conducting this research, the students are trained in methods pertaining to both inorganic chemistry and biology. The research experiences provide the students with skills useful in many areas of chemical and biological research and prepare them for careers in STEM.
