Effects of protein folding on metalloprotein redox-active sites: electron-transfer properties of blue and purple copper proteins

The tuning of the electron-transfer properties of the metal sites in blue a nd purple copper proteins by the protein fold is reviewed, with azurin and the Thermus Cu-A domain as examples. These proteins have unique electronic and EPR spectra, which are ascribed to highly electron-delocalized metal si tes. The folding free energies of these proteins are higher in the oxidized compared to the reduced states, and as a consequence the reduction potenti als of the unfolded proteins are higher than those of the native forms. The high potentials of the unfolded proteins are ascribed tb maintenance of th e core ligand structure of the metal site. In proteins with the folded form s having a higher potential than the unfolded forms, the potential is incre ased by hydrophobic encapsulation. In proteins with a lower potential of th e folded forms, the high potential is down-tuned by different strengths of axial ligation, controlled, by the protein fold. (C) 1999 Elsevier Science S.A. All rights reserved.