Redox-active centers electron transfer

The possibility that there might be long-range electron transfer between redox-active centers in enzymes was first suspected by biochemists working on the mechanism of action of metalloenzymes such as xanthine oxidase which contain more than one metal-based redox center. In these enzymes electron transfer frequently proceeds rapidly but early spectroscopic measurements, notably those by electron paramagnetic resonance, failed to provide any indication that these centers were close to one another. 

Many proteins are exclusively involved in intra-protein electron transfer and typically function in ordered structures such as mitochondria. Under these circumstances, the redox-active centers are generally accessible on the outer surface of the protein. In contrast, the redox reactions catalyzed by oxidoreductases involve small molecules with the reaction involving two redox couples, i.e. the substrate and the co-factor or co-substrate. Because the catalytic center of the enzyme is often located... 

Figure 3. The three-state hypothesis for the redox potentials of electron transfer in the 4Fe-4S active centers of ferredoxins and HiPIP (7). The redox potential differs over a 1-V range (see also Ref. 2 for discussion).

Xanthine is converted to uric acid at the molybdenum center of the enzyme, and the electrons are removed from the enzyme by oxidation of the flavin center. From early reductive titrations of xanthine oxidase with sodium dithionite, it was proposed that reducing equivalents were equilibrated among the four redox-active centers (Mo-co, two separate Fe2S2 centers, flavin) at a rate that was rapid relative to the overall catalytic rate of substrate turnover (243). Under such conditions, the flux of reducing equivalents through the enzyme should be influenced by the relative reduction potentials of the redox centers involved (244). Any effects of pH and temperature on the reduction potentials of individual redox components would affect the apparent rates of intramolecular transfer of the enzyme. 

Studies on the electrochemical behavior of ferrocene encapsulated in the hemi-carcerands 61 and 62, indicated that encapsulation induces substantial changes in the oxidation behavior of the ferrocene subunit [98]. In particular, encapsulated ferrocene exhibits a positive shift of the oxidation potential of c. 120 mV, probably because of the poor solvation of ferrocenium inside the apolar guest cavity. Lower apparent standard rate constants were found for the heterogeneous electron transfer reactions, compared to those found in the uncomplexed ferrocene under identical experimental conditions. This effect may be due to two main contributions (i) the increased effective molecular mass of the electroactive species and (ii) the increased distance of maximum approach of the redox active center to the electrode surface. 

CuA-centers are found in cytochrome c oxidases and in N20-reductase [40,41]. In both enzyme classes, CuA-centers subtract electrons from an external donor and transfer them either directly to the active site or indirectly via a further redox-active center [42-44]. Until recently, knowledge concerning the structure of CuA-centers was incomplete. This situation was alleviated by the publication of the crystal-structures of cytochrome c oxidase from Paracoccus denitrificans and bovine heart in 1995 [43,44]. According to these data, CuA-centers contain [2Cu-2S] structures similar to those in [2Fe-2S]-type iron-sulfur clusters. Both sulfur ligands are donated by cysteine residues in the peptide chain and form a planar structure with the copper ions [43-45]. In both structures, an electron can be delocalized over both metal-ions. In the iron-sulfur center this effect is observed in the reduced form [FeZ5+-Fe2 5+], while in the CuA-center the delo-... 

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