Redox-active prosthetic groups

Electron transfer (ET) is a key reaction in biological processes such as photosynthesis and respiration [1], Photosynthetic and respiratory chain redox proteins contain one or more redox-active prosthetic groups, which may be metal complexes or organic species. Since it is known from crystal structure analyses that the prosthetic groups often are located in the protein interior, it is likely that ET in protein-protein complexes will occur over large molecular distances ( > 10 A) [2-4],... 

Fe S-containing enzymes frequently have other redox-active prosthetic groups, notably, flavins FAD or FMN. Likewise, the redox partner for many Fe S proteins is a flavoprotein this provides a convenient mechanism for turning a one-electron transfer reaction into a two-electron donor/acceptor. Hence, the structures elucidating the interactions between Fe S clusters and other cofactors are of considerable interest. At present there are only two examples for which we have crystallographic structures, yet both provide a basis to propose possible mechanisms for electron transfer to Fe S clusters. 

With the exception of the recently reported DMSO reductases from bacteria (71,72), all of the enzymes of Table I contain additional redox active prosthetic groups besides Mo-co. Substrate oxidation (reduction) occurs at the molybdenum center, and electrons are removed (added) via one of the other prosthetic groups. These two processes are coupled by intramolecular electron transfer between the molybdenum center and the other redox centers of the enzyme. Results for xanthine oxidase and sulfite oxidase and approaches to modeling the coupling in sulfite oxidase are summarized below. 

Flavoenzymes are widespread in nature and are involved in many different chemical reactions. Flavoenzymes contain a flavin mononucleotide (FMN) or more often a flavin adenine dinucleotide (FAD) as redox-active prosthetic group. Both cofactors are synthesized from riboflavin (vitamin B2) by microorganisms and plants. Most flavoenzymes bind the flavin cofactor in a noncovalent mode (1). In about 10% of aU flavoenzymes, the isoalloxazine ring of the flavin is covalently linked to the polypeptide chain (2, 3). Covalent binding increases the redox potential of the flavin and its oxidation power, but it may also be beneficial for protein stability, especially in flavin-deficient environments. 

Because of their large protein structures, enzymes can usually only slowly exchange electrons with the electrode. Therefore, at least in the case of redox-active prosthetic groups, a redox catalyst has usually to be added to accelerate the turnover by speeding up the electron exchange between the enzyme respectively the cofactor and the electrode. However, sometimes the direct electron transfer to and from a redox enzyme can be performed by activation of the electrode surface using promoter molecules or by certain electrode modifications by the enzymes [20]. 

FAD is a redox-active prosthetic group commonly found at the active site of oxidase enzymes. A related species, flavin mononucleotide (FMN) is present at the active sites of many dehydrogenase enzymes. What these two prosthetic groups... 

Four protein complexes, three ofthem function as proton pumps, are embedded in the inner mitochondrial membrane and constitute essential components of the electron transport chain. Every complex consists of a different set of proteins with a variety of redox-active prosthetic groups. AU in all, through oxidation of NADH, a proton gradient between the matrix and the intermembrane space is created, which eventually drives the ATP synthase-complex. The correspondingly released electrons are consumed in the reduction of oxygen to water. Both, the NADH oxidation and the oxygen reduction, as well as the ATP synthesis, take place in the matrix of the mitochondrion (Fig. 8.14). 

It should be possible to overcome such problems by direct electron transfer between the redox-active prosthetic group of an enzyme and the elec-... 

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