Novel tripeptide model of nickel superoxide dismutase.
Nickel superoxide dismutase (Ni-SOD) catalyzes the disproportionation of superoxide to molecular oxygen and hydrogen peroxide, but the overall reaction mechanism has yet to be determined. Peptide-based models of the 2N:2S nickel coordination sphere of Ni-SOD have provided some insight into the mechanism of this enzyme. Here we show that the coordination sphere of Ni-SOD can be mimicked using the tripeptide asparagine-cysteine-cysteine (NCC). NCC binds nickel with extremely high affinity at physiological pH with 2N:2S geometry, as demonstrated by electronic absorption and circular dichroism (CD) data. Like Ni-SOD, Ni-NCC has mixed amine/amide ligation that favors metal-based oxidation over ligand-based oxidation. Electronic absorption, CD, and magnetic CD (MCD) data collected for Ni-NCC are consistent with a diamagnetic Ni(II) center bound in square-planar geometry. Ni-NCC is quasi-reversibly oxidized with a midpoint potential of 0.72(2) V (vs Ag/AgCl) and breaks down superoxide in an enzyme-based assay, supporting its potential use as a model for Ni-SOD chemistry.
Krause
Mary E
ME
Department of Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
Glass
Amanda M
AM
Jackson
Timothy A
TA
Laurence
Jennifer S
JS
D032701:Biomimetics; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D013482:Superoxide Dismutase / Q000737:chemistry*
D009842:Oligopeptides; D009532:Nickel; D013482:Superoxide Dismutase