The biochemical principles of life are based on both organic and inorganic chemistry. My laboratory focuses on the inorganic biochemical aspects, namely how the nutritionally essential transition metal ions maintain human life and how they support growth and development. Manganese, iron, copper, and zinc ions are constituents of thousands of proteins and function in enzymatic catalysis and protein structure. Transition metal ions regulate protein functions and proteins regulate their availability. For these activities, proteins employ dynamic coordination environments that link metal ion binding and protein conformational changes.
Cellular metal ion homeostasis requires multiple proteins for transport, sensing, chaperoning, and other functions in a network of tightly controlled interactions and with full integration into metabolism and signaling. The metal-regulatory proteins employ specific molecular mechanisms. One mechanism is the sulfur-ligand centered reactivity in zinc/thiolate coordination environments. Sulfur donors confer redox activity on the otherwise biologically redox-inert zinc ion. This coupling between zinc and redox metabolism provides a way of controlling zinc binding and protein functions.
Fundamental insights into the control of transition metal ion homeostasis will lead to an understanding of the pharmacological activity and toxic actions of metal ions, and aid in developing strategies for optimizing human health and for preventing, diagnosing, and treating human diseases.