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Controlling metal-catalyzed protein oxidation

Controlling metal-catalyzed protein oxidation in biology and medicine

The Danish Council for Independent Research | Technology and Production Sciences - Grant: DKK 6,465,888

Project period: 01.03.2015 - 28.02.2018


Summary

Metal ions, reactive oxygen species and irreversible protein oxidation are all heavily involved in many
diseases and human ageing. We intend to investigate what conformational changes are induced by
metal-catalyzed oxidation (MCO) and how they lead to misfolding and/or aggregation using proteins
important in human health and biotechnology – alpha-synuclein (Parkinson’s disease), Clostridium
difficile Toxin B, Cu,Zn-superoxide dismutase (Amyotrophic Lateral Sclerosis) and two milk proteins.

We will first test the hypothesis that MCO damage occurs adjacent to metal binding sites. We will then
test whether it is possible to predict and modify metal binding sites, or introduce decoy binding sites,
and in that way control the effects of MCO in complex systems like the diseased cell or an industrial
production system. Finally, as proof-of-principle, we will test whether introduction of a decoy metalbinding
site to an abundant native protein can control oxidative damage in an animal model system.

Please click figure for larger version.


Other members of the research team

  • Professor Morten J. Bjerrum, University of Copenhagen
  • Professor Michael J. Davies, University of Sydney
  • Principal Investigator René Jørgensen, Statens Serum Institut
  • Associate Professor Thomas J.D. Jørgensen, University of Southern Denmark
  • Professor Daniel Otzen, Aarhus University