Structure to function relationships in ceruloplasmin: a 'moonlighting' protein

  title={Structure to function relationships in ceruloplasmin: a 'moonlighting' protein},
  author={P Bielli and Lilia Calabrese},
  journal={Cellular and Molecular Life Sciences CMLS},
Abstract. 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 multicopper oxidase evolved to insure a safe handling of oxygen in some metabolic pathways of vertebrates. The presently available knowledge of its structure provides a glimpse of its plasticity, revealing a multitude of binding sites… 

Looking for a partner: ceruloplasmin in protein–protein interactions

The essential role of CP in iron metabolism in humans is particularly evident in the case of loss-of-function mutations in the CP gene resulting in a neurodegenerative syndrome known as aceruloplasminaemia.

The Possible Role of GPI-Ceruloplasmin in Hypoxia De Novo Creation and Maintenance

It is postulate that the regulation of GPI-Cp could be the molecular event in the creation and the maintenance of hypoxia in tumor cells, and it would appear possible to attempt to overcome tumor Hypoxia, thus improving the efficiency of radiotherapy.

Multicopper oxidases: an innovative approach for oxygen management of aerobic organisms

It is proposed that the regulation of GPI-ceruloplasmin isoform, present on the surface of the plasma membrane, could be the molecular event in the creation and the maintenance of hypoxia in tumor cells, and by silencing the different MCO genes with siRNA, it would appear possible to attempt to overcome tumor hypoxIA, thus improving the efficiency of radiotherapy.

[Ceruloplasmin, hephaestin and zyklopen: the three multicopper oxidases important for human iron metabolism].

The distribution of multi-copper ferroxidases in many tissues ensures the proper iron turnover in the body as well as preventing toxic effects related to the presence of Fe2+ ions.

Laccases of prokaryotic origin: enzymes at the interface of protein science and protein technology

This review aims to present an update of current knowledge on prokaryotic multicopper oxidases, with a special emphasis on laccases, anticipating their enormous potential for industrial and environmental applications.

Metals in the “omics” world: copper homeostasis and cytochrome c oxidase assembly in a new light

The current knowledge on copper homeostasis and the assembly of cytochrome c oxidase are reviewed to exemplify the kind of important processes which need to be studied at the system level.

Metallo-oxidase Enzymes: Design of their Active Sites

Substrate specificities are determined primarily by the nature of a substrate docking/oxidation (SDO) site associated with the T1 Cu centre and this is the focus of this review.

The biology of mammalian multi-copper ferroxidases.

The mammalian multicopper ferroxidases (MCFs) ceruloplasmin (CP), hephaestin (HEPH) and zyklopen (ZP) comprise a family of conserved enzymes that are essential for body iron homeostasis. Each of



Ceruloplasmin: the copper transport protein with essential oxidase activity.

  • E. FriedenH. Hsieh
  • Biology
    Advances in enzymology and related areas of molecular biology
  • 1976
Ceruloplasmin, the blue copper-protein of vertebrate plasma, has been reviewed mainly from a functional point of view, but the chemistry and state copper in the molecule are surveyed because of the implications of the recent data of Ryden (13,28).

The multifunctional oxidase activity of ceruloplasmin as revealed by anion binding studies.

The data presented are consistent with a mechanism of structural and functional modulation of CP by anions, that would be able to dictate the substrate specificity of the cuproprotein, and suggest the possibility that CP may act in vivo as a multifunctional oxidase.

Ceruloplasmin has a distinct active site for the catalyzing glutathione-dependent reduction of alkyl hydroperoxide.

It is reported that human ceruloplasmin exhibits an alkyl hydroperoxide peroxidase activity, which is independent of the oxidase activity.

Homology modeling of the multicopper oxidase Fet3 gives new insights in the mechanism of iron transport in yeast.

The surface disposition of negatively charged residues suggests that Fet3 can translocate Fe(3+) to the permease Ftr1 through a pathway under electrostatic guidance.

Structural comparison of cupredoxin domains: Domain recycling to construct proteins with novel functions

Simultaneous structural superposition of the enzyme domains and their known cupredoxin relatives shows clearly that there are at least six cupredoxins classes, and that the evolution of the conserved core of these domains is independent of the presence or absence of copper sites.

Crystal structure of the type-2 Cu depleted laccase from Coprinus cinereus at 2.2 Å resolution

The structure of laccase from the fungus Coprinus cinereus has been determined by X-ray crystallography at a resolution of 2.2 Å and is a monomer composed of three cupredoxin-like β-sandwich domains, similar to that found in ascorbate oxidase.

Structure and function of copper-containing proteins

  • E. Adman
  • Biology, Chemistry
    Current Biology
  • 1992

Identification of the prooxidant site of human ceruloplasmin: a model for oxidative damage by copper bound to protein surfaces.

Observations support the hypothesis that Cu bound at specific sites on protein surfaces can cause oxidative damage to macromolecules in their environment.

Labile conformation of type 2 Cu2+ centres in human ceruloplasmin.

1. The investigation of human ceruloplasmin by spectral methods (EPR and spectrophotometry) demonstrated that type 2 Cu2(+)-containing centres occur not in one, but in two stable forms, differing in