Binding copper

Abolmaali B, Taylor HV, Weser U (1998) Evolutionary Aspects of Copper Binding Centers in Copper Proteins. 91 91-190... 

Menkes Disease Is Due to Mutations in the Gene Encoding a Copper-Binding P-Type ATPase... 

The cause of Wilson disease was also revealed in 1993, when it was reported that a variety of mutations in a gene encoding a copper-binding P-type ATPase were responsible. The gene is estimated to encode a protein of 1411 amino acids, which is highly homologous to the product of the gene affected in Menkes disease. In a manner not yet fully explained, a nonfunctional ATPase causes defective excretion of copper into the bile, a reduction of incorporation of copper into... 

Ceruloplasmin contains substantial amounts of copper, but albumin appears to be more important with regard to its transport. Both Wilson disease and Menkes disease, which reflect abnormahties of copper metabohsm, have been found to be due to mutations in genes encoding copper-binding P-type ATPases. 

Umezawa, H., Takita, T.. The Bleomycins Antitumor Copper-Binding Antibiotics. Vol. 40, pp. 73-99. 

Rao, S. B. K., A. M. Tyryshkin et al. (2000). Inhibitory copper binding site on the spinach cytochrome bf complex Implications for Q0 site catalysis. Biochemistry 39 3285-3296. 

Wang, J., Xu, G., Gonzales, V. et al. Fibrillar inclusions and motor neuron degeneration in transgenic mice expressing superoxide dismutase 1 with a disrupted copper-binding site. Neurobiol. Dis 10 128-138,2002. 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

There is considerable similarity between domains 1, 3, and 5 with excellent matching of the (3-strands 168 a-carbon atoms of domain 3 and 149 atoms of domain 5 can be superimposed on domain 1 with a root mean square fit of only 1.0 A. Major deviations occur in the loops between the first and second, and the fourth and sixth strands. The similarity of the smaller mononuclear copper binding domains, 2,4, and 6, is even more pronounced with 147 atoms from domain 4 and 143 from domain 6 fitting domain 2 with a root mean square deviation of only 0.9 A in each case. However, although all 6 domains are based on a cupre-doxin-type fold, the various loop regions deteriorate the match between an even and an odd domain with a typical fit of 1.8 A for only 91 atoms when domain 2 is superposed onto domain 1. The superposition results are summarized as part of Table 2. 

Figure 2. The cupredoxin fold in (a) the odd and (b) the even domains of hCP. The P-barrels comprise two sheets of P-strands. Sheet 1 involves strands 2a, 8, 7, and 4 and the four type I copper binding residues emanate from this sheet (see Table 3). Sheet 2 involves strands 2a, 1, 3, and 6.

Table 3. Sequence Alignment for Copper Binding Sitesa,b c,d (3-Strand 4 Domains which do NOT bind mononuclear copper... 

It is interesting to speculate why nitrite reductase has its type I coppers in domains 1, whereas in hCP the mononuclear copper binding sites are retained in the domains 2,4, and 6 where they are comparatively buried in the protein. One possible reason can be related to the difference in functions of the two proteins. NR has to interact with a relatively large pseudo-azurin macromolecule in order for electron transfer to take place,... 

In freshwater algae, movement of copper into cells occurs mainly by physical transport the plasmalemma is the initial site of copper binding. Copper on the plasmalemma increases its permeability, as shown by the leakage of potassium and other ions from copper-treated cells and entry of copper into intracellular sites (Stokes 1979). 

Earthworms from soils heavily contaminated with copper (2740 mg/kg DW soil) can regulate copper more efficiently than cadmium and lead. However, copper is more toxic to earthworms than lead or zinc in the soil, due, in part, to the inability of most soft tissues to synthesize copper-binding ligands when challenged with copper (Morgan and Morgan 1990). 

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