Copper proteins roles

The many redox reactions that take place within a cell make use of metalloproteins with a wide range of electron transfer potentials. To name just a few of their functions, these proteins play key roles in respiration, photosynthesis, and nitrogen fixation. Some of them simply shuttle electrons to or from enzymes that require electron transfer as part of their catalytic activity. In many other cases, a complex enzyme may incorporate its own electron transfer centers. There are three general categories of transition metal redox centers cytochromes, blue copper proteins, and iron-sulfur proteins. 

The size and complexity of the hCP molecule are consistent with a multifunctional role for this protein in the plasma, although its precise functions, as yet, remain unclear for this reason it has been termed the enigmatic copper protein [3], Most of the functions that have been ascribed focus on the presence of the copper centers (see for example refs. 4 and 5), and the major roles can be summarized as follows ... 

The need for a Greek key fold remains obscure. The apoproteins are clearly stable without metals there are examples other than immunoglobulins of Greek key folds. So far copper seems to be found in a very limited subset of structures other chapters in this volume show that zinc, for example, has a much wider variety of environments in proteins, as does iron. It may be that the copper-containing Greek key proteins represent a very small evolutionary niche. Structures of other copper proteins will undoubtedly reveal new surprises and help to clarify the essential role of copper in biological systems. 

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 ability to obtain accurate redox potentials has played a key role in the investigation of copper proteins since it has provided investigators with data from which to generate an understanding of the factors giving rise to the unusually high potentials exhibited by some... 

Blue copper proteins are a family of metalloproteins that have been found to play an important role in a number of electron-transfer reactions in nature. Solomon and coworkers have studied a range of blue copper enzymes in detail to produce a thorough description of how molecular and electronic structure interact to provide the function of these enzymes (26,158). 

The expression for the contribution to the spin-orbit induced MCD intensity from perturbation of the ground state is somewhat reminiscent of an expression for the Ag quantity of EPR spectroscopy. The similarity lies in the paramagnetic term, Agp. This term is composed of integrals of a spin-orbit operator over molecular orbitals similar to the expression for the perturbation of the ground state in the presence of spin-orbit coupling (Eqs. 52-56). The paramagnetic contribution to Ag dominates for blue copper proteins and it was suspected that the MCD parameters and Amay have some sort of relationship. It was found that many of the terms that make large contributions to AgP do play a role in the MCD intensity but no simple relationship was found (160). 

Cass, A. E, G., Hill, H. A. O. Copper proteins and copper enzymes. In Biological Roles of Copper, Ciba Foundation Symposium 79, Amsterdam-Oxford-New York, Excerpta Medica, 1981, in press... 

Structure-function roles have been suggested for unique tryptophan residues in other copper proteins as well (44,45, 46). Moreover, the single tryptophan that is quenched by including the copper atom in azurin is apparently not in contact with the indole ring, as evidenced by metal replacement and phosphorescence results (45, 46). 

What distinguishes multicopper oxidases from other copper proteins is that they contain one each of these three types of copper site (Solomon and Lowery, 1993 Solomon et al., 1996). Not only does this make them excellent models for all copper proteins, but because they have four redox-active metal ions, they also serve as paradigms for other enzymes that couple a one-electron reductant to a four-electron oxidant, most notably cytochrome c oxidase. Indeed, the three copper sites (and four copper atoms) in the multicopper oxidases play essentially equivalent roles in comparison to the two heme groups and two copper atoms in cytochrome c oxidase. 

Copper proteins can fill quite different biological roles. In each case, the function is determined by the three-dimensional structure of the biomolecule as well as by the coordination geometry of the metal site, which in turn determines the electronic structure of the metal ion(s) (Bertini et al., 1993c, 1994a Holm et al., 1996 Solomon et al., 1992). 

This is an auspicious time to publish a volume on copper proteins. The number of known proteins with metallic cofactors continues to increase steadily, and the availability of structural and sequence data is enabling much more specihc characterizations of the interactions between the metal ions and proteins as well as of their functions and mechanisms. Numerous investigators are choosing copper proteins and copper metabolism as their model systems for such studies. While copper-containing proteins play essential roles, their numbers are few enough that a comprehensive understanding is a reasonable goal. 

Husain, M., and Davidson, V. L., 1985, An inducible periplasmic blue copper protein from Paracoccus denitrificans. Purification, properties and physiological role, J. Biol. Chem. 260 14626nl4629. 

Blue copper proteins have been purified and biochemically characterized from Archaea, Bacteria, and Eukarya. Such ubiquitous distribution suggests an important ancient role. A survey of sequence databases reveals genes encoding blue copper proteins that display characteristics often quite different from those of well-studied canonical (traditional) blue copper proteins. For example, there are modular proteins where the domains that bind type 1 copper are fused with structurally distinct and evolutionarily unrelated sequence motifs (Figure 1). While these additional domains do not usually contribute directly to the ftmction of a blue copper protein, they do so indirectly by facilitating protein translocation to a specific cellular compartment. Together, these blue copper proteins can be combined into a large superfamily which can be subdivided into three classes as described below. 

The substitution of other metal ions for copper has played an important role in spectroscopic studies of the type 1 copper proteins. For example, Mn(n), Co(II), and Ni(II) derivatives proved useful in analyzing their electronic absorption spectra and Cd(II) substitution has been used to examine the metal binding sites through Cd NMR spectroscopy. ... 

Once inside the mucosal cell, iron then has to be transported across the membrane to serum transferrin. This appears to take place via the Iregl transporter protein (also known as ferroportin 1 or MTPl). Iregl is a transmembrane protein located at the basolateral membrane of the cell that has been shown to be involved in iron uptake. Oxidation of Iregl-bound ferrous iron and its release to transferrin is likely to be enhanced by the membrane-bound multicopper ferroxidase hephaestin. This protein is 50% identical to ceruloplasmin, a soluble protein identified as having a possible role in iron loading of transferrin see Copper Proteins Oxidases). Mutation of hephaestin in mice leads to a build up of iron in duodenal cells and overall iron deficiency in the body. ... 

---