Copper reductases

A substantial fraction of the named enzymes are oxido-reductases, responsible for shuttling electrons along metabolic pathways that reduce carbon dioxide to sugar (in the case of plants), or reduce oxygen to water (in the case of mammals). The oxido-reductases that drive these processes involve a small set of redox active cofactors , that is, small chemical groups that gain or lose electrons. These cofactors include iron porjDhyrins, iron-sulfur clusters and copper complexes as well as organic species that are ET active. 

Pereira MM, Santana M, Teixeira M. 2001. A novel scenario for the evolution of haem-copper oxygen reductases. Biochim Biophys Acta 1505 185. 

R. Welch, W. Norvell, S. Schaefer, J. Shaff, and L. Kochian, Induction of iron (111) and copper (11) reduction in pea Pisiim. sativum L.) roots by Fe and Cu status. Does the root-cell plasma Fe(lll) reductase perform a general role in regulating cation uptake Planta 190 555 (1993). 

Under conditions of copper deficiency, some methanotrophs can express a cytosolic, soluble form of MMO (sMMO) (20-23), the properties of which form the focus of the present review. The sMMO system comprises three separate protein components which have all been purified to homogeneity (24,25). The hydroxylase component, a 251 kD protein, contains two copies each of three subunits in an a 82y2 configuration. The a subunit of the hydroxylase houses the dinuclear iron center (26) responsible for dioxygen activation and for substrate hydroxylation (27). The 38.6 kD reductase contains flavin adenine dinucleotide (FAD) and Fe2S2 cofactors (28), which enable it to relay electrons from reduced nicotinamide adenine dinucleotide (NADH) to the diiron center in the... 

To provide a model for nitrite reductases72 Karlin and co-workers characterized a nitrite-bound complex (226) (r = 0.05)214 In an endeavor to model nitrite reductase activity, Tanaka and co-workers prepared a few mononuclear complexes (227) (r = 0.74)215 (228) (r = 0.82),216 (229) (r = 0.97),217 (230) (r = 0.16),217 (231) (r = 0.07),217 and (232) (r = 0.43 and r = 0.53)217 and studied the electrochemical reduction of N02A As a part of their activity on modeling heme-copper terminal oxidases, Holm and co-workers prepared complex (233) (r = 0.96).218 Using a sterically hindered tris(pyridylmethyl)amine, Canary et al. prepared a complex (234) (r=1.00), studied its redox behavior, and discussed various factors that may contribute to the difference (higher potential for the new complex) in the redox potential of a Cu Cu1 couple between substituted and unsubstituted ligands.2 9... 

Figure 8.3 A model of iron transport across the intestine. Reduction of ferric complexes to the ferrous form is achieved by the action of the brush border ferric reductase. The ferrous form is transported across the brush border membrane by the proton-coupled divalent cation transporter (DCT1) where it enters an unknown compartment in the cytosol. Ferrous iron is then transported across the basolateral membrane by IREG1, where the membrane-bound copper oxidase hephaestin (Hp) promotes release and binding of Fe3+ to circulating apotransferrin. Except for hephaestin the number of transmembrane domains for each protein is not shown in full. Reprinted from McKie et al., 2000. Copyright (2000), with permission from Elsevier Science.

Fig. 6.9 The catalysts for denitrification. Nitrate is reduced by a molybdenum enzyme while nitrite and oxides of nitrogen are reduced today mainly by copper enzymes. However, there are alternatives, probably earlier iron enzymes. The electron transfer bct complex is common to that in oxidative phosphorylation and similar to the bf complex of photosynthesis, while cytochrome c2 is to be compared with cytochrome c of oxidative phosphorylation. These four processes are linked in energy capture via proton (H+) gradients see Figure 6.8(a) and (b) and the lower parts of Fig. 6.9 which show separately the active site of the all iron NO-reductase, and the active site of cytochrome oxidase (02 reductase).

Nitric oxide reductase (P) Nitrous oxide reductase (P) Ascorbate oxidase (P) Cytochrome oxidase (PM) Copper ATPase pumps (PM)... 

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,... 

Several copper enzymes will be discussed in detail in subsequent sections of this chapter. Information about major classes of copper enzymes, most of which will not be discussed, is collected in Table 5.1 as adapted from Chapter 14 of reference 49. Table 1 of reference 4 describes additional copper proteins such as the blue copper electron transfer proteins stellacyanin, amicyanin, auracyanin, rusticyanin, and so on. Nitrite reductase contains both normal and blue copper enzymes and facilitates the important biological reaction NO) — NO. Solomon s Chemical Reviews article4 contains extensive information on ligand field theory in relation to ground-state electronic properties of copper complexes and the application of... 

The NO/NO+ and NO/NO- self-exchange rates are quite slow (42). Therefore, the kinetics of nitric oxide electron transfer reactions are strongly affected by transition metal complexes, particularly by those that are labile and redox active which can serve to promote these reactions. Although iron is the most important metal target for nitric oxide in mammalian biology, other metal centers might also react with NO. For example, both cobalt (in the form of cobalamin) (43,44) and copper (in the form of different types of copper proteins) (45) have been identified as potential NO targets. In addition, a substantial fraction of the bacterial nitrite reductases (which catalyze reduction of NO2 to NO) are copper enzymes (46). The interactions of NO with such metal centers continue to be rich for further exploration. 

Interest in this class of coordination compounds was sparked and fueled by the discovery that radical cofactors such as tyrosyl radicals play an important role in a rapidly growing number of metalloproteins. Thus, in 1972 Ehrenberg and Reichard (1) discovered that the R2 subunit of ribonucleotide reductase, a non-heme metal-loprotein, contains an uncoordinated, very stable tyrosyl radical in its active site. In contrast, Whittaker and Whittaker (2) showed that the active site of the copper containing enzyme galactose oxidase (GO) contains a radical cofactor where a Cu(II) ion is coordinated to a tyrosyl radical. 

The next five transition metals iron, cobalt, nickel, copper and zinc are of undisputed importance in the living world, as we know it. The multiple roles that iron can play will be presented in more detail later in Chapter 13, but we can already point out that, with very few exceptions, iron is essential for almost all living organisms, most probably because of its role in forming the amino acid radicals required for the conversion of ribonucleotides to deoxyribonucleotides in the Fe-dependent ribonucleotide reductases. In those organisms, such as Lactobacilli6, which do not have access to iron, their ribonucleotide reductases use a cobalt-based cofactor, related to vitamin B12. Cobalt is also used in a number of other enzymes, some of which catalyse complex isomerization reactions. Like cobalt, nickel appears to be much more extensively utilized by anaerobic bacteria, in reactions involving chemicals such as CH4, CO and H2, the metabolism of which was important... 

Figure 3.13 Structure of the Cuz centre in nitrous oxide reductase. The central sulfide interacts with all four copper atoms. (From Rees, 2002. Copyright 2002 Annual Reviews.)...

Figure 7.4 Copper uptake and release in E. hirae. The extracellular reductase CorA reduces Cu2+ to Cu+ for uptake by CopA. In conditions of copper excess CopB functions as a copper exporter. (From Solioz and Stoyanov, 2003. Reproduced with permission from Blackwell Publishing Ltd.)...

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