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Controlling metal-catalyzed protein oxidation in biology and medicine

Project: Research

  • Møller, Ian Max (Participant)
  • Bjerrum, Morten (Participant)
  • Davies, Michael J (Participant)
  • Jørgensen, René (Participant)
  • Jørgensen, Thomas J. D. (Participant)
  • University of Copenhagen
  • Statens Serum Institute
  • University of Southern Denmark
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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 A/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-ofprinciple,
we will test whether introduction of a decoy metal-binding site to an abundant native protein can control oxidative damage in an animal model system.
Effective start/end date01/09/201501/08/2018

ID: 129016242