Structural Biochemistry/Protein function/Ligand/Metal Binding Sites
The ability of a protein to bind metal ligands is often essential to a protein’s function. Furthermore, recent studies have indicated the existence of a new type of protein-metal interaction in which the metal confers a particular function to the protein. Using the familiar example of hemoglobin and its heme group, this new type of interaction would be analogous to attaching a heme group to a protein not naturally possessing one to allow that protein to transport oxygen. In addition, many metals have the ability to induce a conformational change in the protein that they bind to, thus altering its function once again.
A practical application of this concept is the creation of amyloid mimetics. Because of their strength and mechanical stiffness, amyloids are attractive compounds for the construction of nanomaterials. This can be done by employing peptides with a secondary structure of alpha helices and a primary structure containing amino acids with metal-ligating side chains such as His and Cys. When metals such as Cu(II) or Zinc(II) are introduced, they will bind as ligands at the center of the helix to create the desired nanomaterials. This process can be taken further by creating a coil within a coil. This is usually done using heavy metals such as Pb and As, and results in a diverse array of nanomaterials. Alternatively, peptides can be designed to interact with a metal in a desired way, thus yielding different structures and functions. For example, addition of Cd(II) may induce a conformation in which there are four connections to the metal, whereas addition of Cu(I) may only form two connections with that same peptide.
Another area of interest involving protein-metal interaction is the affinity of certain proteins for inorganic substrates in the solid state such as metals and carbon. This type of behavior has been observed in the formation of pearls, as well as in bones and tooth enamel in humans. Although a definitive relationship between protein affinity and substrate identity has not yet been established, certain observations pervade this phenomenon. For example, proteins with an affinity for Ag substrates tend to contain proportionally larger amounts of Ser and Pro, whereas proteins with an affinity for C (nanotubes) tend to contain proportionally larger amounts of Typ and His. Another observed trend is the affinity of unfolded proteins for Au and the affinity of folded proteins for Pt.
Protein-metal interaction is also being studied in green fluorescent protein (GFP). The concept is to create a “metal sensor” by combining the easy visibility of fluorescent compounds with the ability of proteins to bind metal ligands. Through modification of GFP, variations of GFP can be created that are specifically designed to bind a certain number of a certain metal atom, thus the amount of GFP will correspond to the unknown amount of metal ions in the sample solution. Recent studies indicate that the best results are with metals in the 2+ oxidation state, particularly Zn(II), with the exception of Ca(II) and Mg(II).