title: Dioxygen and superoxide stability of metallopeptide based mimics of nickel containing superoxide dismutase: the influence of amine/amidate vs. bis-amidate ligation.
abstract: Nickel containing superoxide dismutase (NiSOD) is a metalloenzyme that catalyzes the disproportionation of O2(-). In its reduced state, the Ni(II) ion is coordinated by two cis-cysteinates, an amine nitrogen and an amidate nitrogen atom. It thus bears a resemblance to the distal bis-cysteinate bis-amidate ligated nickel center of acetyl coenzyme A synthase. Using metallopeptide based NiSOD mimics derived from the first 12 residues of the NiSOD sequence we demonstrate that altering the primary coordination sphere from a bis-thiolate amine/amidate motif to a bis-thiolate bis-amidate motif changes the O2 and ROS stability of the metallopeptide. Using FT-IR, ESI-MS and S K-edge XAS we show that the bis-amidate bis-thiolate ligated metallopeptide {Ni(II)(SOD(m1)-Ac)} (SOD(m1)-Ac=AcHN-HCDLPCGVYSPA-COOH) undergoes oxidation at one thiolate ligand in the presence of O2, converting it into a coordinated sulfinate. Upon exposure of {Ni(II)(SOD(m1)-Ac)} to O2(-) the metallopeptide undergoes extensive sulfur oxidation. This can be contrasted with the unacylated metallopeptide {Ni(II)(SOD(m1))} which does not undergo sulfur based oxidation under these conditions. The biological implications of these findings are discussed.
authors.affiliation: Department of Chemistry, University of Nevada, Reno, Reno, NV 89557-0216, USA. Electronic address: shearer@unr.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Shearer
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry*; D008667:Metalloproteins / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry; D013482:Superoxide Dismutase / Q000737:chemistry*
chemical_list: D008667:Metalloproteins; D010455:Peptides; D017382:Reactive Oxygen Species; D009532:Nickel; D013482:Superoxide Dismutase; D010100:Oxygen
keywords: ESI-MS; FT-IR; NiSOD; S K-edge XAS