Structural and functional characterization of protein-metal interactions.

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Metal-protein interactions play crucial roles in regulating a number of biological processes, and there is considerable interest in characterizing the mechanistic details of these important interactions. For example, metals such as calcium, copper, iron and zinc play key biological roles through specific interactions with select proteins, and these interactions are essential for the survival of many organisms including humans, bacteria and plants. In addition to these essential metals, there are also metals commonly present in high concentrations in our environment that are toxic by virtue of their ability to associate with cellular proteins and disrupt their normal biological functions. Toxic metals that pose a serious threat to both our health and environment include mercury, lead, tin, cadmium and arsenic. For the last twenty-five years, my laboratory has been characterizing the interaction of proteins with both essential and toxic metals. The long-term objectives of our research program are to structurally and functionally characterize protein-metal interactions involving both essential and toxic metals. In particular, we are interested in how essential metals help proteins fold into their functional conformation as well as how toxic metals can disrupt the normal processes involving essential metals. Currently, there are several ongoing investigations in the laboratory examining protein-metal interactions. For example, we are examining how thioester metabolites of commonly used lipid lowering and non-steroidal anti-inflammatory drugs disrupt essential protein-metal interactions in human cells. We are also examining protein-metal interactions involved in biomineralization that have potential applications to the production of synthetic silver-based nanomaterials for use in such diverse products as electronics, optics or as antimicrobial agents. In addition, we are examining the interaction of a number of toxic metals such as mercury, tin and lead with bacterial proteins to determine how these bacterial proteins might be better used to develop efficient bioremediation systems that utilize green chemistry for removing these extremely toxic metals from our environment. The proposed combination of structural and functional studies on protein-metal interactions that we undertaking will have an important impact on our understanding of a number of crucial biochemical and bioorganic mechanisms that will have applications to toxic metal remediation, nanomaterial production as well as our understanding of toxicities associated with commonly used drug agents.