Ceruloplasmin structural studies

Lindley, P. E, Card, G., Zaitseva, I., Zaitsev, V., Reinhammar, B., Selin-Lindgren, E., and Yoshida, K. (1997). An X-ray structural study of human ceruloplasmin in relation to ferroxidase activity./. Biol. Inorg. Chem. 2, 454 63. 

Studies of other sources of ceruloplasmin may eventually prove useful in structure elucidation, but have already clarified some of the copper chemistry. Ceruloplasmin from goose serum has been isolated, purified, and characterized. This ceruloplasmin has less carbohydrate attached, but two forms may be isolated under some conditions. It is clear that these are not products of proteolytic degradation, but perhaps they might have a different carbohydrate attached. The two type I sites have higher extinction coefficients than type I sites in other ceruloplasmins, reflecting a modestly different environment (Hilewicz-Grabska et al, 1988). 

Catalytic reaction schemes for laccase and ceruloplasmin have been formulated on the basis of the mechanistic studies and the state of characterization of the copper redox centers at this time. They are outlined in the reviews on laccase by Reinhammar (10) and on ceruloplasmin by Ryden (26). The degree of correctness of these reaction schemes is rather limited due to the fact that the structure and spatial arrangement of the copper centers were unknown at this time. 

P16. Poulik, M. D., Electrophoretic and immunological studies on structural subunits of human ceruloplasmin. Nature 194, 842-844 (1962). 

Intramolecular ET between distinct copper centers is part of the catalytic cycles of many copper-containing redox enzymes, such as the multicopper oxidases, ascorbate oxidase, and ceruloplasmin, as well as the copper-containing nitrite reductases. Examination of internal LRET in these proteins is of considerable interest as it may also provide insights into the evolution of selected ET pathways in particular, whether and how the enzymes have evolved in order to optimize catalytic functions. With the increase in the number of known high-resolution 3D structures of transition metal containing redox enzymes, studies of structure-reactivity relationships have become feasible and indeed many have been carried out during the last two decades. 

A basic tenet in biology is that structure and function are linked, and the model above is consistent with functional studies on heme uptake from and gene regulation by heme-hemopexin (see below), Thus, with the recent details of the structures of hemopexin (M. Paoli, H. M. Baker, B. F. Anderson, W. T. Morgan, A. Smith, N. Baker, unpublished results) and ceruloplasmin [74], the metal-protein interactions of two key players in redox metal transport and metabolism are now established. 

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