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Authors
White, Kenneth N.Conesa, Celia
Sánchez, Lourdes
Amini, Maryam
Farnaud, Sébastien
Lorvoralak, Chanakan
Evans, Robert W.
Affiliation
London Metropolitan UniversityUniversidad de Zaragoza
Brunel University
University of Westminster
Issue Date
2012-03-28
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It is over 60years since the discovery and isolation of the serum ferroxidase ceruloplasmin. In that time much basic information about the protein has been elucidated including its catalytic and kinetic properties as an enzyme, expression, sequence and structure. The importance of its biological role is indicated in genetic diseases such as aceruloplasminemia where its function is lost through mutation. Despite this wealth of data, fundamental questions about its action remain unanswered and in this article we address the question of how ferric iron produced by the ferroxidase activity of ceruloplasmin could be taken up by transferrins or lactoferrins. Overlapping peptide libraries for human ceruloplasmin have been probed with a number of different lactoferrins to identify putative lactoferrin-binding regions on human ceruloplasmin. Docking software, 3D-Garden, has been used to model the binding of human lactoferrin to human ceruloplasmin. Upon probing the human ceruloplasmin library with human lactoferrin, three predominantly acidic lactoferrin-binding peptides, located in domains 2, 5 and 6 of human ceruloplasmin, were identified. The docking software identified a complex such that the N-lobe of human apo-lactoferrin interacts with the catalytic ferroxidase centre on human ceruloplasmin. In vitro binding studies and molecular modelling indicate that lactoferrin can bind to ceruloplasmin such that a direct transfer of ferric iron between the two proteins is possible. A direct transfer of ferric iron from ceruloplasmin to lactoferrin would prevent both the formation of potentially toxic hydroxyl radicals and the utilization of iron by pathogenic bacteria. BACKGROUND METHODS RESULTS GENERAL SIGNIFICANCECitation
White KN, Conesa C, Sánchez L, Amini M, Farnaud S, Lorvoralak C, Evans RW (2012) 'The transfer of iron between ceruloplasmin and transferrins', BBA - Biochimica et Biophysica Acta, 1820 (3), pp.411-6.Publisher
ElsevierPubMed ID
22040722Additional Links
https://www.sciencedirect.com/science/article/pii/S0304416511002509Type
ArticleLanguage
enISSN
0006-3002EISSN
0006-3002ae974a485f413a2113503eed53cd6c53
10.1016/j.bbagen.2011.10.006
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