Question

Suppose you want to design a biological transport protein for copper. Propose a reasonable active site and strategy that differs from transferrin to bind and release the copper ion from the protein. Be sure to specify the oxidation state(s).

Answer 1

For designing a biological transport protein, we can take a similar approach as that of chaperones. Chaperones are copper-binding proteins. Cytosolic copper means the copper ions found inside the intracellular fluid. These small copper-binding proteins help in maintaining cytosolic copper below very low concentrations. This results in preventing damage to non-specific proteins. It is because chaperones prevent copper binding to these non-specific proteins. Chaperones are involved in transport across the membrane of the endoplasmic reticulum. The region of an enzyme where substrate molecules undergo reaction after binding is called active site. Since protein synthesis occurs generally in the area of endoplasmic reticulum, chaperones are found near this organelle. The active site must be a copper-dependent enzyme. One such enzyme is superoxide dismutase 1. It is located on chromosome 21. It helps in binding both copper and zinc ions.

Let us look at copper delivery to superoxide dismutase 1.  The protein that contains the metal ion cofactor is called metalloprotein. CCS is a metalloprotein. It is the copper chaperone for superoxide dismutase 1. This is a 54-kDa metalloprotein. The strategy includes three domains: N-terminus domain I, domain II and domain III.  MXCXXC copper-binding motif is the first domain. This is the stage of identification and characterization. The second domain is complementary to the superoxide dismutase 1 structure. This is recognition and binding stage. Third domain involves copper exchange with superoxide dismutase 1. This stage also involves disulfide oxidation. This includes CXC copper-binding motif.

Oxidation states are specified below:

superoxide dismutase- -2

copper ion- +2