An X-ray structural study of human ceruloplasmin in relation to ferroxidase activity

  • P. F. Lindley
  • Graeme Card
  • Irina Zaitseva
  • Vjacheslav Zaitsev
  • Bengt Reinhammar
  • Eva Selin-Lindgren
  • Kunihiro Yoshida
ORIGINAL ARTICLE

Abstract

 The role of ceruloplasmin as a ferroxidase in the blood, mediating the release of iron from cells and its subsequent incorporation into serum transferrin, has long been the subject of speculation and debate. However, a recent X-ray crystal structure determination of human ceruloplasmin at a resolution of around 3.0 Å, in conjunction with studies associating mutations in the ceruloplasmin gene with systemic haemosiderosis in humans, has added considerable weight to the argument in favour of a ferroxidase role for this enzyme. Further X-ray studies have now been undertaken involving the binding of the cations Co(II), Fe(II), Fe(III), and Cu(II) to ceruloplasmin. These results give insights into a mechanism for ferroxidase activity in ceruloplasmin. The residues and sites involved in ferroxidation are similar to those proposed for the heavy chains of human ferritin. The nature of the ferroxidase activity of human ceruloplasmin is described in terms of its three-dimensional molecular structure.

Key words Ceruloplasmin Ferroxidase Iron Metabolism Copper transport 

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Copyright information

© Society of Biological Inorganic Chemistry 1997

Authors and Affiliations

  • P. F. Lindley
    • 1
  • Graeme Card
    • 1
  • Irina Zaitseva
    • 1
  • Vjacheslav Zaitsev
    • 1
  • Bengt Reinhammar
    • 2
  • Eva Selin-Lindgren
    • 3
  • Kunihiro Yoshida
    • 4
  1. 1.CCLRC Daresbury Laboratory, Warrington, Cheshire WA4 4AD, UKGB
  2. 2.Department of Biochemistry and Biophysics, Lundberg Laboratory, University of Göteborg, Medicinaregatan 9C, S-413 90 Göteborg, SwedenSE
  3. 3.Department of Physics, Chalmers University of Technology, S-412 96 Göteborg, SwedenSE
  4. 4.Department of Medicine (Neurology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390, Japan and Gene Targetting Research and Core Facility, National Institute of Dental Research, National Institutes of Health, Building 30/Room 529, Bethesda, MD 20892-4326, USAJP

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