Redox proteins cytochromes

Ribbon structures of two redox proteins, cytochrome c (a) and plastocyanin (b). The blowups show the active sites where transition metal atoms are located. 

K.J. McKenzie and F. Marken, Accumulation and reactivity of the redox protein cytochrome c in mes-oporous films of Ti02 phytate. Langmuir 19, 4327-4331 (2003). 

The redox protein cytochrome c dissolved in both [BMPrl][H2P04] and [H0EtMe3N][H2P04] [87] indicating that a hydrogen-bonding capability of the cation is not required, in contrast with the above example. FT-IR measurements showed that cyt c maintained its native secondary structure upon dissolution in these ionic liquids. 

We have investigated in-situ STM of the small single-metal redox proteins cytochrome c (MW 12 kDa) and azurin ( 14 kDa), and the larger four copper-enzyme laccase (MW 64 kDa), all involved in natural ET [51, 54, 55]. The choice rested on the following considerations ... 

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. 

In some cases, small biological redox partner proteins such as heme-containing cytochromes, ferredoxins comprising an iron-sulfur cluster, or azurin with a mononuclear Cu site have been used as natural mediators to facilitate fast electron exchange with enzymes. A specific surface site on the redox protein often complements a region on the enzyme surface, and enables selective docking with a short electron tunneling... 

The catalytic activity of CYP enzymes requires functional coupling with its redox partners, cytochrome P450 NADPH oxidoreductase (OR) and cytochrome bs. Measurable levels of these two proteins are natively expressed in most cell lines. Therefore, introduction of only the CYP cDNA is generally needed for detectable catalytic activity. However, the levels of expression of the redox partner proteins may not support maximal CYP catalytic activity, and therefore enhancement of OR levels may be desirable. This approach has been used successfully with an adenovirus expression system in LLC-PKi cells [12],... 

The first reports on direct electrochemistry of a redox active protein were published in 1977 by Hill [49] and Kuwana [50], They independently reported that cytochrome c (cyt c) exhibited virtually reversible electrochemistry on gold and tin doped indium oxide (ITO) electrodes as revealed by cyclic voltammetry, respectively. Unlike using specific promoters to realize direct electrochemistry of protein in the earlier studies, recently a novel approach that only employed specific modifications of the electrode surface without promoters was developed. From then on, achieving reversible, direct electron transfer between redox proteins and electrodes without using any mediators and promoters had made great accomplishments. 

Most mechanisms which control biological functions, such as cell respiration and photosynthesis (already discussed in Chapter 5, Section 3.1), are based on redox processes. In particular, as shown again in Figure 1, it is evident that, based on their physiological redox potentials, in photosynthesis a chain of electron carriers (e.g. iron-sulfur proteins, cytochromes and blue copper proteins) provides a means of electron transport which is triggered by the absorption of light. 

Figure 8.1. Redox proteins catalyzing electron transfer from hydrogen to sulfate in Desulfovibrio. The cytoplasmic uptake of protons associated with the reduction of sulfate is not shown. Hyd, hydrogenase cyctcs, cytochrome C3 HmcA, HmcB, HmcC, HmcE, HmcF, components of the Hmc complex IM, inner membrane OM, outer membrane.

The preceding discussion of cytochromes c provides most detail on eukaryotic, mitchondrial cytochromes c, a small subset of this huge superfamily. Additionally, all the cytochromes c discussed in this section envelop one heme cofactor, although many cytochromes in nature contain more than one heme cofactor. Many other redox proteins contain a cytochrome c domain—a few of these mentioned here include the cytochrome bci complex discussed in Section 7.6, cytochrome c oxidase to be discussed in Section 7.8, and cytochrome c peroxidase, discussed briefly in Section 7.7 (see especially Section 7.7.4.2). 

The final group of mitochondrial redox components are one-electron carriers, small proteins (cytochromes) that contain iron in the form of the porphyrin complex known as heme. These carriers, which are discussed in Chapter 16, exist as several chemically distinct types a, b, and c. Two or more components of each type are present in mitochondria. The complex cytochrome aa3 deserves special comment. Although cytochromes are single-electron carriers, the cytochrome aa3 complex must deliver four electrons to a single 02 molecule. This may explain why the monomeric complex contains two hemes and two copper atoms which are also able to undergo redox reactions.1 2... 

An example is adrenodoxin reductase (see chapter banner, p. 764), which passes electrons from NADPH to cytochrome P450 via the small redox protein adrenodoxin. This system functions in steroid biosynthesis as is indicated in Fig. 22-7.209a b Other flavin-dependent reductases have protective functions catalyzing the reduction of ascorbic acid radicals,210 211 toxic quinones,212-214 and peroxides.215-218... 

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