The Science Seminar Series: February 12, 2009
Modeling the Active Site of Nickel-Containing Superoxide Dismutase: A New Role for Nickel in Biology.
Todd C. Harrop
Department of Chemistry
University of Georgia
Place: Powell Hall
Time: 4:00 -5:00pm
The anionic superoxide radical is an inevitable product of aerobic respiration, which if not eliminated, may cause significant cell damage implicating this molecule in a variety of disorders. In order to combat such oxidative stress, all aerobic organisms possess metalloenzymes known as superoxide dismutases (SODs) that catalyze the disproportionation of superoxide to peroxide and molecular oxygen. Most recently, a new class of SODs has been discovered from Streptomyces soil bacteria and cyanobacteria that contain nickel at the active site. In contrast to other known SODs, Ni-SOD contains a square-planar Ni(II) ion ligated in an N2S2 environment consisting of one deprotonated peptide-N, one primary amine-N from the N-terminal histidine residue, and two cysteine-S donors. Ni-SOD is also unlike any other Ni-protein present in biology. In order to gain a fundamental understanding of the properties and mechanism of catalysis of this unique metallocenter, our lab has developed synthetic routes towards molecular structures analogous to the active site of Ni-SOD. The synthesis, structure, and reactive properties of Ni complexes housed in a mixed N,S ligand environment with spatial disposition and electronic features similar to the active site of Ni-SOD will be presented.