ABSTRACT
In this chapter we focus on the roles of the cofactors in folding and stability of copperbinding proteins. Copper (Cu) is essential for the survival of living organisms. It is found in the active sites of proteins that participate in cellular respiration, antioxidant defense, neurotransmitter biosynthesis, connective-tissue biosynthesis, and pigment formation (Huffman and O’Halloran 2001; Puig and Thiele 2002; Harris 2003). In Table 4.1 we list the major types of proteins that bind Cu, along with their functional role; we also give some examples of their structures (Figure 4.1). After iron, Cu is the second most common element in biological systems to participate in electrontransfer chains. The thermodynamic and kinetic feasibility of Cu to oxidize/reduce (switching between Cu1+ and Cu2+) allows copper-containing proteins to play important roles as electron carriers and redox catalysts in living systems. How and when is the metal inserted into these proteins in the cell? Since non-bonded Cu ions are toxic due to their ability to catalyze the formation of harmful free radicals, the intracellular concentration of Cu is highly regulated (O’Halloran and Culotta 2000). Both prokaryotic and eukaryotic cells regulate Cu homeostasis via dedicated proteins that facilitate its uptake, efflux, as well as distribution to target proteins/enzymes.
