Electron transfer in metalloproteins

The metalloproteins consist of a metal complex imbedded in and bonded to a protein net of covalently bonded amino acids. The most commonly studied systems are the myoglobins and cytochromes, which contain Fe(II) or Fe(III) in a porphyrin complex, or the copper blue proteins, which have Cu(II) or Cu(I) compiexed most often by histidine nitrogens and cysteine and methionine sulfurs from the protein. Metalloproteins can be oxidized or reduced by standard transition-metal complex reagents, and the latter usually are chosen to ensure outer-sphere electron transfer. This area has been the subject of numerous reviews. 

In these systems, the oxidant and reductant typically are linked by a largely saturated protein chain, with chain lengths of 10 to 20 A. Thus, the systems have an analogy to the weakly coupled bimetal systems discussed in the previous section. The distance dependence of the rate of electron transfer has been investigated using modified proteins in which, typically, Ru (NH3)5 is attached at a specific site then, it is reduced to Ru(II) and the rate of electron transfer from the latter to the metal in the protein is measured. 

The interpretation of the kinetic results on these systems has revolved around the distance dependence, as discussed in the previous section. Dutton and co-workers first noted a correlation with Ae distance, r A, between donor and acceptor, of the following form  

However, a study of Ru-modified myoglobins gave the following smaller dependence on distance  

At present, there is still debate about the importance of the hopping and direct or superexchange mechanisms for these systems. The model of Beratan and Onuchic suggests that hydrogen bonding within the peptide chain facilitates the superexchange pathway, but observations by 

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Therlen MJ, Chang J, Raphael AL, Bowler BE, Gray HB (1991) Long-Range Electron Transfer in Metalloproteins. 75 109-130... 

Long-Range Electron Transfer in Metalloproteins M. J. Therien, J. Chang, A. L. Raphael, B. E. Bowler,... 

Early attempts at observing electron transfer in metalloproteins utilized redox-active metal complexes as external partners. The reactions were usually second-order and approaches based on the Marcus expression allowed, for example, conjectures as to the character and accessibility of the metal site. xhe agreement of the observed and calculated rate constants for cytochrome c reactions for example is particularly good, even ignoring work terms. The observations of deviation from second-order kinetics ( saturation kinetics) allowed the dissection of the observed rate constant into the components, namely adduct stability and first-order electron transfer rate constant (see however Sec. 1.6.4). Now it was a little easier to comment on the possible site of attack on the proteins, particularly when a number of modifications of the proteins became available. 

The mechanism of the regulation of electron transfer in metalloproteins has been investigated 61) and two relevant examples have been discussed in the first one the molecular mechanism controlling the electron transfer reactions is restricted to the immediate chemical environment of the metal center (azurin), while in the second one it involves a conformational transition of the whole quaternary structure of the enzyme. The power of the kinetic approach in detecting significant intermediates was emphasized 6t>. The Cu metal complex site of azurin has a distorted tetrahedral... 

Chang IJ, Gray HB, Winkler JR. High-driving-force electron-transfer in metalloproteins - intramolecular oxidation of ferrocytochrome-c by Ru(2,2 -bpy)2(lm)(His-33)3+. J Am Chem Soc 1991 113 7056-7. 

The ability to exist in more than one oxidation state allows transition-metal complexes to serve as the active site of enzymes whose function is to transfer electrons (39). A great deal of effort has been directed at understanding the mechanisms of electron transfer in metalloproteins, such as cytochromes and blue copper proteins (40). Of particular interest is the mechanism by which an electron can tunnel from a metal center that is imbedded in a protein matrix to a site on the outer surface of the protein (7). A discussion of current theories is given in this volume. 

Sigel, H. Sigel, A. Electron Transfer in Metalloproteins Marcel Dekker New York, 1991. 

The investigation of the kinetics and mechanisms of electron transfer reactions between metalloproteins and with inorganic redox reactants continues to be a rapidly growing field. The Proceedings of the 3rd International Conference on Bioinorganic Chemistry (1987) have been published in a special issue of Recueil des Travaux Chimiques des Pay-Bas, and include a section on metalloprotein electron transfer. The subject of long-distance electron transfer in metalloproteins has also been reviewed. 

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