AN X-RAY STRUCTURAL STUDY OF HUMAN CERULOPLASMIN IN RELATION TO FERROXIDASE ACTIVITY

The role of ceruloplasmin as a ferroxidase in the blood, mediating the release of iron from cells and its subsequent incorporation into seru m transferrin, has long been the subject of speculation and debate. Ho wever, a recent X-ray crystal structure determination of human cerulop lasmin at a resolution of around 3.0 Angstrom, in conjunction with stu dies associating mutations in the ceruloplasmin gene with systemic hae mosiderosis in humans, has added considerable weight to the argument i n 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 insig hts into a mechanism for ferroxidase activity in ceruloplasmin. The re sidues and sites involved in ferroxidation are similar to those propos ed for the heavy chains of human ferritin. The nature of the ferroxida se activity of human ceruloplasmin is described in terms of its three- dimensional molecular structure.