Copper proteins classification

Since the first EPR work on Cu(II) ions in proteins in the late fifties193, a great many EPR investigations on copper-containing proteins have been reported194-198. For a classification of the copper proteins into type I (blue copper), type II (non-blue copper) and type III (binuclear cupric pair), the reader is referred to Fee197. ... 

This copper-dependent enzyme [EC 1.14.18.1] (also known as tyrosinase, phenolase, monophenol oxidase, and cresolase) catalyzes the reaction of L-tyrosine with L-dopa and dioxygen to produce L-dopa, dopaquinone, and water. This classification actually represents a set of copper proteins that also catalyze the reaction of catechol oxidase [EC 1.10.3.1] if only 1,2-benzenediols are available as substrates. 

Blue copper proteins, 36 323, 377-378, see also Azurin Plastocyanin active site protonations, 36 396-398 charge, 36 398-401 classification, 36 378-379 comparison with rubredoxin, 36 404 coordinated amino acid spacing, 36 399 cucumber basic protein, 36 390 electron transfer routes, 36 403-404 electron transport, 36 378 EXAFS studies, 36 390-391 functional role, 36 382-383 occurrence, 36 379-382 properties, 36 380 pseudoazurin, 36 389-390 reduction potentials, 36 393-396 self-exchange rate constants, 36 401-403 UV-VIS spectra, 36 391-393 Blue species... 

The copper centres in the multicopper blue oxidases have been classified into three groups. This classification may be extended to include other copper proteins. 

Before they were characterized by x-ray crystallography, the classification of the structures of copper proteins was initially based on the spectroscopic features of their active site in the oxidized state. The tremendous development of crystallographic and spectroscopic techniques in recent years has enabled the identification of as many as seven different types of active sites in these proteins type 1, type 2, type 3, type 4, CuA, CuB and Cuz. The characteristics of these metal sites are briefly described below. 

Based on spectroscopic properties, mainly electron paramagnetic resonance (EPR), the active sites of copper proteins have been classified into three groups, types I, II, and III. This nomenclature was originally applied to blue oxidases to distinguish the four copper ions contained in these proteins. The original classification has been extended to the copper sites of other proteins. The recent increase in structural information on the copper sites in proteins has, however, revealed greater diversity in the type of copper site. For instance, the type III and type II sites in ascorbate oxidase are in close proximity, forming a trinuclear site, in which all three copper ions are essential for the reactivity. Some proteins, once believed to contain a copper site with normal spectroscopic properties, and thus referred as type II, have been shown to contain copper coordinated by an unusual side chain. Therefore, in this review, new nomenclature is used to classify the copper sites more precisely with respect to their structural features and spectroscopic properties. The definitions are as follows ... 

One of the major goals of studying active sites in copper proteins has therefore been to understand the spectroscopic features associated with the active site. This has led to a classification of three general types of copper protein active sites based on their unique spectral features Blue copper, normal copper and coupled binuclear copper. An additional class of copper proteins, the multi-copper oxidases, contains a combination of these three types of copper active sites. A reasonably firm understanding of the optical and EPR spectra of a number of copper proteins has now been achieved1,2K This article presents an overview of these electronic spectral features and their relationship to geometric and electronic structure. 

This chapter summarizes some recent developments in the purification of ascorbate oxidase, the number of copper atoms per active molecule, and the stoichiometry of the different copper sites with reference to the classification introduced by Malkin and Malmstrom (5). Furthermore, physical properties of the metal centers are discussed in relation to other simple copper proteins that have been characterized in recent years. Finally, kinetic investigations of ascorbate oxidase reduction are presented as studied by anaerobic stopped-fiow and rapid-freeze techniques. 

Table 1 Classification of copper centers in copper proteins. 

Type 2 Cu2+. This form of Cu is present in all the blue multi-copper oxidases. It is characterized by lacking sufficient optical absorption to be observed above that of the other Cu-chromophores in these molecules. Consequently it is sometimes referred to as the colorless Cu. Further, its EPR spectrum is similar to those exhibited by most small Cu2+ complexes. However, its presence is essential to the functioning of the multi-copper oxidases, and it has very unique chemical properties which distinguish it from Cu + bound to the non-blue Cu proteins. The T5q)e 2 designation should therefore be reserved for classification of the types of Cu2+ sites observed in the blue multi-copper oxidases, and it should not be used to classify the binding sites of non-blue copper proteins which have distinctly different chemical behavior. Thus, for example, any purported analogies between... 

The generally accepted classification of copper proteins is based on their biological functions each class comprises several types, each one of them with similar copper active centres but with some differences in the amino acid sequences of the proteins, for instance. 

Close inspection of currently available sequences of proteins carrying BCB domains clearly indicated that they can be classified into four major classes, which are described below. This classification is based on their ability to bind copper and the specific features of their domain organization. Members of the first three classes harbor single or multiple type 1 blue copper-binding sites, while members of the fourth class do not appear to bind copper. Domain organizations of the precursors of aU currently known protein families that contain a BCB domain are shown in Fig. 1. 

Copper centers in proteins were initially classified into three types (types 1-3, see Table 1). " The classification was based mainly on their spectroscopic features, particularly those in electronic absorption and electron paramagnetic resonance spectra. Since the initial classification, two new copper centers, Cua and Cuz," have been discovered and characterized. Their unique structures do not belong to any of the three known types of copper centers and now those centers form their own classes. 

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