CHAPTER 9: Reinventing the Wheel: The NiSOD Story

The most recently discovered SOD requires nickel in its active site – NiSOD. Among the available metals, nickel seems an unlikely redox center. This chapter discusses the protein adaptations required in order to use nickel for SOD catalysis. Cysteine ligands are employed for the first time in an SOD, to suppress the potential of the Ni(ii/iii) couple. However, this adaptation alone is not sufficient to produce an SOD, since thiolate ligands are sensitive to oxidation by H₂O₂ and O₂. Additional adaptations include the use of two unusual backbone N-donor ligands, an amidate and the N-terminal amine. Yet merely producing a stable Ni redox center is not sufficient for SOD catalysis. A source of protons is needed to produce H₂O₂ and the pH-independent catalysis that is characteristic of SODs. Thus, the cysteine thiolates were also employed to provide a site for protonation. In restricting active site access, NiSOD appears to have utilized the same strategy employed by MnSOD and FeSOD – a “gateway” formed by Tyr residues. Thus, NiSOD represents evolution that converged on the same criteria for catalysis as other SODs, where the adaptations to the metal site are uniquely suited to using nickel as a redox center.