Copper enzymes hemocyanin

Figure 1 Schematic representation of the dioxygen binding dinuclear copper enzymes Hemocyanin (He), Tyrosinase (Tyr), and Catechol oxidase (Co)...

Table 5.2 contains data about selected copper enzymes from the references noted. It should be understood that enzymes from different sources—that is, azurin from Alcaligenes denitrificans versus Pseudomonas aeruginosa, fungal versus tree laccase, or arthropodan versus molluscan hemocyanin—will differ from each other to various degrees. Azurins have similar tertiary structures—in contrast to arthropodan and molluscan hemocyanins, whose tertiary and quaternary structures show large deviations. Most copper enzymes contain one type of copper center, but laccase, ascorbate oxidase, and ceruloplasmin contain Type I, Type II, and Type III centers. For a more complete and specific listing of copper enzyme properties, see, for instance, the review article by Solomon et al.4... 

There are a number of excellent sources of information on copper proteins notable among them is the three-volume series Copper Proteins and Copper Enzymes (Lontie, 1984). A review of the state of structural knowledge in 1985 (Adman, 1985) included only the small blue copper proteins. A brief review of extended X-ray absorption fine structure (EXAFS) work on some of these proteins appeared in 1987 (Hasnain and Garner, 1987). A number of new structures have been solved by X-ray diffraction, and the structures of azurin and plastocyanin have been extended to higher resolution. The new structures include two additional type I proteins (pseudoazurin and cucumber basic blue protein), the type III copper protein hemocyanin, and the multi-copper blue oxidase ascorbate oxidase. Results are now available on a copper-containing nitrite reductase and galactose oxidase. 

Chalcogenides Solid-state Chemistry Copper Enzymes in Denitrification Copper Hemocyanin/Tyrosinase Models Copper Proteins Oxidases Copper Proteins with Dinuclear Active Sites Copper Proteins with Type 1 Sites Copper Proteins with Type 2 Sites Iron Sulfitf Models of Protein Active Sites Iron-Snlfiir Proteins Nickel Enzymes Cofactors Nickel Models of Protein Active Sites Polynuclear Organometallic Cluster Complexes. 

The clinical symptoms of classical Menkes disease can be traced back to developmentaUy important copper enzymes such as lysyl oxidase, tyrosinase (see Copper Hemocyanin/Tyrosinase Models), cytochrome c oxidase (see Cytochrome Oxidase), dopamine -hydroxylase, superoxide dismutase, and amine oxidase (see Superoxide Dismutase). Lysyl oxidase is needed for the cross-linking of connective tissue a deficiency in this enzyme causes weakened connective tissue and connective tissue disorder such as arterial ruptures as observed in these patients. Low levels of cytochrome c oxidase cause temperature instability and the absence of tyrosinase explains the hair depigmentation observed in affected individuals. ... 

Formation of metal-oxo species first became realistic in model studies on heme oxygenases (shunt path), and it has also become popular in nonheme systems. As for the metal-jd-peroxo species, the distinctive example of model study has appeared in the copper enzymes. The type 7 peroxo species has been proposed first based on models for dicopper oxy-hemocyanin [19, 20] before demonstration of the same oxygen bonding in enzyme [13]. The type 7 x-peroxo structure has been applied to diiron species in sMMO [14] in addition to 6 [21]. (see Chapter 8)... 

This discussion of copper-containing enzymes has focused on structure and function information for Type I blue copper proteins azurin and plastocyanin, Type III hemocyanin, and Type II superoxide dismutase s structure and mechanism of activity. Information on spectral properties for some metalloproteins and their model compounds has been included in Tables 5.2, 5.3, and 5.7. One model system for Type I copper proteins39 and one for Type II centers40 have been discussed. Many others can be found in the literature. A more complete discussion, including mechanistic detail, about hemocyanin and tyrosinase model systems has been included. Models for the blue copper oxidases laccase and ascorbate oxidases have not been discussed. Students are referred to the references listed in the reference section for discussion of some other model systems. Many more are to be found in literature searches.50... 

Evidence tom a variety of sources indicates that the active site of tyrosinase is very similar to that of hemocyanin, a dioxygen-binding protein found in molluscs and arthropods (15,16). This type of active site contains two copper ions, which are cuprous in the deoxy state, and which reversibly bind dioxygen, forming the oxy form of the enzyme or protein in which a peroxy ligand bridges between two cupric ions. 

The enzyme requires two copper ions per subunit for full expression of activity (18), but, unlike tyrosinase and hemocyanin, there is an absence of magnetic coupling between the two Cu(II) sites and both appear to be separate, isolated mononuclear copper sites (17). The process of dioxygen binding and activation appears to involve interaction of the doxygen molecule with only one copper ion, and it is also found that a proton is requir for the hydroxylation of substrate (19). 

Copper Essential to all organisms constituent of redox enzymes and hemocyanin." Very toxic to most plants highly toxic to Invertebrates, moderately so to mammals. Pollution from industrial smoke and possibly from agricultural use. Wilson s disease, genetic recessive, results in toxic increase in copper storage. 

Tire most studied of all copper-containing oxidases is cytochrome c oxidase of mitochondria. This multisubunit membrane-embedded enzyme accepts four electrons from cytochrome c and uses them to reduce 02 to 2 H20. It is also a proton pump. Its structure and functions are considered in Chapter 18. However, it is appropriate to mention here that the essential catalytic centers consist of two molecules of heme a (a and a3) and three Cu+ ions. In the fully oxidized enzyme two metal centers, one Cu2+ (of the two-copper center CuA) and one Fe3+ (heme a), can be detected by EPR spectroscopy. The other Cu2+ (CuB) and heme a3 exist as an EPR-silent exchange-coupled pair just as do the two copper ions of hemocyanin and of other type 3 binuclear copper centers. 

Copper has an essential role in a number of enzymes, notably those involved in the catalysis of electron transfer and in the transport of dioxygen and the catalysis of its reactions. The latter topic is discussed in Section 62.1.12. Hemocyanin, the copper-containing dioxygen carrier, is considered in Section 62.1.12.3.8, while the important role of copper in oxidases is exemplified in cytochrome oxidase, the terminal member of the mitochondrial electron-transfer chain (62.1.12.4), the multicopper blue oxidases such as laccase, ascorbate oxidase and ceruloplasmin (62.1.12.6) and the non-blue oxidases (62.12.7). Copper is also involved in the Cu/Zn-superoxide dismutases (62.1.12.8.1) and a number of hydroxylases, such as tyrosinase (62.1.12.11.2) and dopamine-jS-hydroxylase (62.1.12.11.3). Tyrosinase and hemocyanin have similar binuclear copper centres. 

In the following sections, examples of all the classes of reaction given above will be discussed, with emphasis on those that have been well studied. Many of the enzymes involved in these processes are hemoproteins, but non-heme prosthetic groups are important in oxygenases and are also present in some oxidases. Copper is an important metal in this context, and is present in the oxygen transport protein hemocyanin, and in oxidases such as cytochrome oxidase and laccase. Some flavoenzymes are important too, but will not be covered in this discussion. 

---