Flavin adenine dinucleotide model

A model of a flavin-based redox enzyme was prepared.[15] Redox enzymes are often flavoproteins containing flavin cofactors flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). They mediate one- or two-electron redox processes at potentials which vary in a range of more than 500 mV. The redox properties of the flavin part must be therefore tuned by the apoenzyme to ensure the specific function of the enzyme. Influence by hydrogen bonding, aromatic stacking, dipole interactions and steric effects have been so far observed in biological systems, but coordination to metal site has never been found before. Nevertheless, the importance of such interactions for functions and structure of other biological molecules make this a conceivable scenario. 

The simplest example of such reactions is the decarboxylation of pyruvate. Both model and enzyme studies have shown the intermediacy of covalent complexes formed between the cofactor and the substrate. Kluger and coworkers have studied extensively the chemical and enzymatic behavior of the pyruvate and acetaldehyde complexes of ThDP (2-lactyl or LThDP, and 2-hydroxyethylThDP or HEThDP, respectively) . As Scheme 1 indicates, the coenzyme catalyzes both nonoxidative and oxidative pathways of pyruvate decarboxylation. The latter reactions are of immense consequence in human physiology. While the oxidation is a complex process, requiring an oxidizing agent (lipoic acid in the a-keto acid dehydrogenases , or flavin adenine dinucleotide, FAD or nicotinamide adenine dinucleotide , NAD " in the a-keto acid oxidases and Fe4.S4 in the pyruvate-ferredoxin oxidoreductase ) in addition to ThDP, it is generally accepted that the enamine is the substrate for the oxidation reactions. 

The model system that was used to demonstrate the reciprocal relations was adenosine-5 -mononicotinate, which is given in the stacked or interacted conformation in Fig. 6. The temperature effect for this molecule as seen in the circular dichroism spectra is given in Fig. 7, where the reciprocal relations are beautifully apparent. This approach has been used to identify stacked conformations for flavin-adenine dinucleotide and for the oxidized and reduced forms of a- and /3-nicotinamide-adenine dinucleotide. ... 

Flavin nucleotides—flavin adenine dinucleotide (FAD) and flavin mononucleotide (riboflavin-5 -phosphoric acid) (FMN)—as prosthetic groups can either comprise a metal or serve as cofactors without a metal. Electrochemical transformations of FAD and FMN are characterized by strong adsorption. The area occupied by a FAD molecule on a mercury electrode is 280 A, i.e., close to the geometrical dimensions corresponding to the molecular model. Reduction of FAD and FMN proceeds in two reversible... 

Fig. 2.5 Top panel, a Model of a complex between P450 and NADPH-cytochrome P450 oxidoreductase (FOR). A complex of P450 (red) and Mol A of the hinge-deletion mutant of POR(ATGEE), denoted as PORT e [53]). the flavin mononucleotide (FMN) domain (blue) and flavin adenine dinucleotide (FAD) domain (yellow)] and an enlarged view showing the relative orientation of the EMN and heme, b and c Open-book representation of molecular surface at the interface of P450 (b) and the EMN domain of POR (c). Five salt-bridge pairs are shown with same let-...

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