|Title:||The X-ray structure of human serum ceruloplasmin at 3.1A: nature of the copper centres|
|Authors:||I.Zaitseva, V.Zaitsev, G.Card, K.Moshkov, B.Bax, A.Ralph and P.Lindley|
|Reference:||Journal of Biological Inorganic Chemistry, 1996, 1, 15-23|
The key to understanding the modus operandi of a metalloenzyme lies in the determination of its molecular structure, so that this paper, and the subsequent deposition of the structure in the Protein Data Bank (1KCW), is of huge significance. The present structure is good enough to show most structure features, but as always a higher resolution picture would be valuable. For a metalloenzyme with such a large molecular mass, and of some instability, this remains a challenge.Abstract: The X-ray structure of human serum ceruloplasmin has been solved at a resolution of 3.1Å. The structure reveals that the molecule is comprised of six plastocyanine-type domains arranged in a triangular array. There are six copper atoms; three form a trinuclear cluster sited at the interface of domains 1 and 6, and there are three molonuclear sites in domains 2, 4 and 6. each of the mononuclear coppers is coordinated to a cysteine and two histidine residues, and those is domains 4 and 6 also coordinate to a methionine residue; in domaine 2 the methionine is replaced by a leucine residue which may form van der Walls type contacts with the copper. The trinuclear centre and the mononuclear copper in domain 6 form a cluster essentially the same as that found in ascorbate oxidase, strongly suggesting an oxidase role for ceruloplasmin in the plasma.
|Title:||The Protein Data Bank|
|Authors:||H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne|
|Reference:||Reference: Nucleic Acids Research, 28 pp. 235-242 (2000)|
|Notes:||Notes: The Protein Data Bank (PDB) is operated by Rutgers, The State University of New Jersey; the San Diego Supercomputer Center at the University of California, San Diego; and the Center for Advanced Research in Biotechnology of the National Institute of Standards and Technology -- three members of the Research Collaboratory for Structural Bioinformatics (RCSB). The PDB is supported by funds from the National Science Foundation, the Department of Energy, and two units of the National Institutes of Health: the National Institute of General Medical Sciences and the National Library of Medicine|
|Title:||Structure to function relationships in ceruloplasmin: a 'moonlighting' protein.|
|Authors:||P.Bielli and L.Calabrese|
|Reference:||Cellular and Molecular Life Sciences, 2002, 59, 1413-1427|
|Notes:||Specialised copper sites have been recruited during evolution to provide long-range electron transfer reactivity and oxygen binding and activation in proteins destined to cope with oxygen reactivity in different organisms. Ceruloplasmin is an ancient multi-copper oxidase evolved to ensure a safe handling of oxygen in some metabolic pathways of vertibrates. The presently available knowledge of its' structure provides a glimpse of its' plasticity, revealing a multitude of binding sites that point to an elaborate mechanism of multifunctional activity. Ceruloplasmin represents an example of a 'moonlighting' protein that overcomes the one gene-one structure function concept to follow the changes of the organism in its' physiological and pathological conditions.|
|Title:||A Triangular Copper(I) Complex Displaying Allosteric Coop[erativity in Its Electrochemical Behavior and a mixed-Valence Cu(I)-Cu(I)-Cu(II) State with Unusual Temperature-Dependent Behaviour.|
|Authors:||Peter L. Jones, John.C.Jeffery, John. P.Maher, Jon A. McCleverty, Philip H. Rieger, and Michael D. Ward|
|Reference:||Inorg. Chem., 1997, 36, 3088.|
|Notes:||The EPR spectrum of the CuI2CuII complex shows delocalisation of the unpaired electron between two metal centers below 120K; above 160K the unpaired electron is localised, possibly because the increased thermal motion disrupts the p-stacking pathway which facilitates delocalisation at low temperatures.|
|Title:||Pathophysiology and treatment of intimal hyperplasia and vein graft failure|
|Reference:||PhD Thesis, University of London, Dec 2001|
|Notes:|| See the subsequent papers from the research group at
the Bristol Heart Institute:
Sustained increases in homocysteine, copper and ceruloplasmin following coronary artery bypass grafting.
Jeremy JY, Shukla N, Angelini GD, Wan I, Talpahewa SP, Ascione R. Annals of Thoracic Surgery 2002; 74: 1553-1557.
Homocysteine augments the reduction of endothelium dependent relaxation and cGMP formation in diabetic rabbits.
Shukla N, Thompson CS, Angelini GD, Mikhailidis DP, Jeremy JY. Diabetologia 2002: 45: 1325-1331.
Homocysteine and copper interact to markedly inhibit the relaxation of the rabbit corpus cavernosum. New risk factors for angiopathic erectile dysfunction?
Khan M, Thompson CS, Emsley A, Morgan RJ, Angelini GD, Jeremy JY.
British Journal of Urology 1999: 84: 720-724.
Copper interacts with homocysteine to inhibit nitric oxide formation in the rat isolated aorta.
Emsley A, Jeremy JY, Gomes G, Angelini GD, Plane F.
British Journal of Pharmacology 1999; 126: 1034-1040.
|Title:||An Examination of the Role of Caeruloplasmin in the Oxidation of Homocysteine and in the Generation of Reactive Oxygen Species which may Facilitate Vein Graft Damage|
|Reference:||Thesis for Honours MSci Chemistry at Bristol, June 2003|
|Title:||Caeruliplasmin, copper ions and angiogenesis|
|Authors:||K.S.Raju, G.Allessandri, M. Ziche and P.M.Gullino|
|Reference:||J.National Cancer Institute, 1982, 69, 1183-1188|
|Title:||Oxygen Binding, Activation, and Reduction to Water by Copper Proteins|
|Authors:||Edward I. Solomon, Peng Chen, Markus Metz, Sang-Kyu Lee and Amy E. Palmer|
|Reference:||Angewandte Chemie, International Edition., 2001, 40, 4570-4590|
|Notes:||An excellent review of the details for the proteins and enzymes involved in reversible oxygen binding (hemocyanin), activation (tyrosinase), and four electron reduction (multicopper oxidases). "These oxygen intermediates exhibit unique spectroscopic features indicative of new geometric and electronic structures involved in oxygen activation. The spectroscopic and quantum mechanical study of these intermediates has defined geometric and electronic structure/function correlations, and developed detailed reaction coordinates for the reversible binding of O2, hydroxylation, and H-atom abstraction from different substrates, and the reductive cleavage of the O-O bond in the formation of water"|
|Title:||Electron Microscope study on human ceruloplasmin|
|Authors:||T.G.Samsonidze, K.A.Moshkov, N.A.Kiselev and S.A. Niefakh|
|Reference:||International J. Peptide Protein Research, 1979, 14, 161-168|
|Notes:||Abstract: Electron microscopy of human ceruloplasmin (CP) molecules revealed a few distinctive types of particle images. Analysis of these images allows to propose a tentative model for CP: six "subunits" (which we call domains) not much different in size are arranged with 32 point group pseudosymmetry. The determination of the number of polypeptides arising at the spontaneous specific proteolytic fragmentation of CP and their molecular weights conform with this assumption. The electrophoretic studies of the samples, prepared both with and without potent proteolytic inhibitor, PMSF, revealed that CP is a single chain protein with molecular weight of 130,000. Isolated and stored without PMSF the polypetide chain of CP undergoes specific proteolytic cleavage which results in the appearance of polypeptides with molecular weights of 16,000, 48,000 and 64,000. The latter two polypeptides degradate to about two- and three-fold decreased molecular weight fragments respectively. Therefore, the single polypeptide chain of CP contains at least five peptide bonds which are particularly susceptible to proteolytic attack and which connect six principal segments of the chain. The hydrolysis of these bonds results in liberation of the six fragments which were integrated in the enzymatically active globule of CP.|
|Title:||To be completed|
|Title:||X-ray structures and mechanistic implications of three functional derivatives of ascorbate oxidase from zucchini. Reduced, peroxide and azide forms.|
|Authors:||A. Messerschmidt, H. Luecke and R. Huber|
|Reference:||Journal of Molecular Biology, 1993, 230, 997-1014|
|Title:||Crystal Structure of a Laccase from the Fungus Trametes versicolor at 1.9Å Resolution Containing a Full Complement of Coppers|
|Authors:||Klaus Piontek, Matteo Antorini and Thomas Choinowski|
|Reference:||Journal of Biological Chemistry, 2002, 277(40), 37663-37669|
|Notes:||Described as "the first crystal structure of an active laccase containing a full complement of coppers", i.e. 4|
|Title:||Electron Paramagnetic Resonance Spectrum of Human Serum Copper|
|Authors:||T.Kakuda, H.Tanaka, E.Kimoto, and F. Morishige|
|Reference:||Applied Spectroscopy, 1980, 34, 276-280|
|Notes:||The electron paramagnetic resonance signal of the cupric ion (its perpendicular component) at 77K was found to be different in shape in human blood plasma and serum. On the addition of acid, substrate of ceruloplasmin, reducing agent, or denaturing agent, serum exhibited a complex electron paramagnetic resonance spectrum similar to that of copper diethyldithiocarbamate complex in an organic solvent, with a simultaneous disappearance of the cupric ion signal. Such an electron paramagnetic resonance spectrum occured only from human serum but not from animal (guinea pig, mouse, rat, cattle, or monkey) serum|