Copper in proteins

Copper in proteins is not usually accompanied by any other cofactors such as hemes or inorganic sulfur in iron-containing proteins, so that the... 

Before the unique spectral features of copper in proteins can be discussed, the geometric and electronic structures of normal copper must be considered. In an octahedral environment the cupric ion, which has nine d electrons, would possess a degenerate 2Eg electronic ground state (Fig. 1, left). A geometric distortion which removes this degeneracy would produce a more stable electronic structure, in accordance with the Jahn-Teller... 

Copper in proteins may be present in two oxidation states, copper(l) or copper(ll). In a few systems where multicopper centers are present, mixed valence states can be found. As copper proteins are involved in electron transfer processes or catalyze oxidative reactions, both oxidation states are physiologically relevant, and their characterization is crucial to an understanding of the protein function. 

Mercury is known to substitute for copper in proteins, especially at blue copper sites because of the cysteinyl ligation (40). Such substitution may be helpful in selectively substituting copper sites in multi-copper enzymes, such as laccase, thereby allowing the nature and function of the individual copper centers to be more clearly revealed. 

Davies P, Brown DR (2008) The chemistry of copper binding to PrP is there sufficient evidence to elucidate a role for copper in protein function Biochem J 410 237-244... 

On the basis of spectroscopic properties, copper in proteins are classified into four main types, three involving copper(II) and one involving copper(I), with the proviso that any given type does not necessarily imply "identical coordination spheres or even similar properties" [6]. 

Enzymes often need for their activity the presence of a non-protein portion, which may be closely combined with the protein, in which case it is called a prosthetic group, or more loosely associated, in which case it is a coenzyme. Certain metals may be combined with the enzyme such as copper in ascorbic oxidase and selenium in glutathione peroxidase. Often the presence of other metals in solution, such as magnesium, are necessary for the action of particular enzymes. 

Copper is required for all forms of aerobic and most forms of anaerobic life. In humans, the biological function of copper is related to the enzymatic action of specific essential copper proteins (66). Lack of these copper enzymes is considered a primary factor in cerebral degeneration, depigmentation, and arterial changes. Because of the abundance of copper in most human diets, chemically significant copper deficiency is extremely rare (67). 

Copper is an essential trace element. It is required in the diet because it is the metal cofactor for a variety of enzymes (see Table 50—5). Copper accepts and donates electrons and is involved in reactions involving dismu-tation, hydroxylation, and oxygenation. However, excess copper can cause problems because it can oxidize proteins and hpids, bind to nucleic acids, and enhance the production of free radicals. It is thus important to have mechanisms that will maintain the amount of copper in the body within normal hmits. The body of the normal adult contains about 100 mg of copper, located mostly in bone, liver, kidney, and muscle. The daily intake of copper is about 2—A mg, with about 50% being absorbed in the stomach and upper small intestine and the remainder excreted in the feces. Copper is carried to the liver bound to albumin, taken up by liver cells, and part of it is excreted in the bile. Copper also leaves the liver attached to ceruloplasmin, which is synthesized in that organ. 

Blue copper proteins. A typical blue copper redox protein contains a single copper atom in a distorted tetrahedral environment. Copper performs the redox function of the protein by cycling between Cu and Cu. Usually the metal binds to two N atoms and two S atoms through a methionine, a cysteine, and two histidines. An example is plastocyanin, shown in Figure 20-29Z>. As their name implies, these molecules have a beautiful deep blue color that is attributed to photon-induced charge transfer from the sulfur atom of cysteine to the copper cation center. 

Copper salts such as CuS04 are potent catalysts of the oxidative modification of LDL in vitro (Esterbauer et al., 1990), although more than 95% of the copper in human serum is bound to caeruloplasmin. Cp is an acute-phase protein and a potent inhibitor of lipid peroxidation, but is susceptible to both proteolytic and oxidative attack with the consequent release of catalytic copper ions capable of inducing lipid peroxidation (Winyard and... 

We have already described the link between the uptake of iron and copper in yeast (Chapter 4). Iron uptake by yeast requires two proteins (Dancis et al., 1994 Askwith... 

For biomolecular S = 1/2 systems subject to central hyperfine interaction the intermediate-field situation (B S S I) is not likely to occur unless the micro-wave frequency is lowered to L-band values. When v = 1 GHz, the resonance field for g = 2 is at B = 357 gauss. Some Cu(II) sites in proteins have Az 200 gauss, and this would certainly define L-band EPR as a situation in which the electronic Zeeman interaction is comparable in strength to that of the copper hyperfine interaction. No relevant literature appears to be available on the subject. An early measurement of the Cun(H20)6 reference system (cf. Figure 3.4) in L-band, and its simulation using the axial form of Equation 5.18 indicated that for this system... 

Many multiple copper containing proteins (e.g., laccase, ascorbate oxidase, hemo-cyanin, tyrosinase) contain so-called type III copper centers, which is a historical name (cf. Section 5.8 for type I and type II copper) for strongly exchange-coupled Cu(II) dimers. In sharp contrast to the ease with which 5=1 spectra from copper acetate are obtained, half a century of EPR studies on biological type III copper has not produced a single triplet spectrum. Why all type III centers have thus far remained EPR silent is not understood. 

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,... 

---