Flavin mononucleotide 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. 

Although charge transfer in macromolecules is of fundamental interest and has been studied piecemeal, often with model systems, this field is in its infancy. DNA and RNA complexes have been discussed in Section III. D. The oxidized and reduced forms of flavin mononucleotide produce charge-transfer complexes as precursors of the semiquinone free radical... 

Earlier, we found that heavy-atom effect can also be observed in bioluminescent systems 3,4 bioluminescence inhibition coefficients were found to decrease in the series potassium halides KC1, KBr, and KI. Two mechanisms can be responsible for the change of the intensity of bioiuminescence in the presence of heavy ions the physicochemical effect of external heavy atom mentioned above, and the biochemical effect, i.e. interactions with the enzymes resulting in changes in enzymatic activity. A series of model experiments was conducted to evaluate the contribution of the physicochemical mechanism. These involved the photoexcitation of model fluorescent compounds close to bioiuminescence emitters in chemical nature and fluorescent properties - flavin mononucleotide, firefly luciferin and coelenteramide. These results are clear evidence of the smaller contribution of the physicochemical mechanism to the decrease in the bioiuminescence intensity for the three bioluminescent systems under study.4... 

Some of the flavoproteins which catalyse the reduction of bioreductive drugs show redox-controlled catalysis. The most important of these is probably NADPHxytochrome P-450 reductase, a one-electron donor [147]. At the simplest level, such proteins can be modelled by reduced flavin mononucleotide, FMNHa [148]. 

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... 

Several strategies to increase the production of electron shuttles have been developed to improve the MFC performance in the model exoeleetrogens. For Shewanella species, flavins (riboflavin and flavin mononucleotide) are the most well-known self-secreted electron shuttles. Using deletion mutants lacking various Mtr-associated proteins, the significance of the Mtr extracellular respiratory pathway for the reduction of flavins has been demonstrated. The decaheme cytochromes found on the outer surface of the cell (MtrC and OmcA) are required for the majority of Mtr-associated proteins activity. Weakly acidic pH resulted in poor performance of the MFC and low riboflavin concentrations in the bacterial cultures, while enhanced electrochemical activity of riboflavin was reported at alkaline pH. The increase of riboflavin biosynthesis by Shewanella at the alkaline condition underlies the improvement in the electricity output in MFCs. ... 

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-...

Fig. 2.6 A cartoon representation of a model for POR-P450 complex formation in the endoplasmie reticulum (ER) membrane. Flavin mononucleotide (FMN) domain, flavin adenine dinueleotide FAD) domain, and P450s are shown in blue, yellow, and red balls, respeetively. (1) Multiple P450s exist in the ER membrane. Nucleotide binding favors formation of the elosed form, similar to the one found in the erystal strueture [36]. (2) Upon binding to pyridine nueleotide (NADPH), the enzyme adopts the elosed form. In the elosed form, hydride transfer, inter-...

Fig. 2.14 Interface of the NADPH-cytochrome P450 oxidoreductase (POR)-flavin mononucleotide (FMN) domain—P450 2B4 eomplex. The model was generated as previously described, using mutagenesis constraints...

Figure 11. The pathway of biological desulfurization of model compound dibenzothiophene relies on biocatalysts for specificity. NADH is reduced nicotinamide adenosine dinucleotide FMN is flavin mononucleotide DSZA, DSZB, DSZC, and DSZD are the catalytic gene products of dszA, dszB, dszC, and dszD, respectively...

Figure 8 Illustration of the ensemble of 10 E. coli Flavodoxin structures obtained from homology modeling using distance geometry, superimposed on the crystal structure (heavy line) so as to minimize the coordinate differences to the alpha carbons in residues 4-170. Only the heavy backbone and aromatic sidechain atoms are shown, together with those of the flavin mononucleotide cofactor (lower left)...

Studies with these model systems have shown that the transport of riboflavin at low (e.g., micromolar) concentrations is temperature- and energy-dependent (it is inhibited by inhibitors of ATP production from energy substrates), it becomes saturated as the concentration of riboflavin increases, and it is sodium ion dependent. These characteristics are shared with many other types of small molecules that are actively transported across the gut wall. More specifically for riboflavin, the active transport mechanism involves phosphorylation (to riboflavin phosphate, also known as flavin mononucleotide, or FMN) followed by dephosphorylation, both occurring within the intestinal cells (Figure 1). This latter process is not shared by several other B vitamins, but it is one of a number of common strategies which the gut may use to entrap essential nutrients, and then relocate them, in a controlled manner and direction. A similar strategy is employed at other... 

Lin, L.Y., Sulea, T, Szittner, R., Vassilyev, V, Purisima, E.O., and Meighen, E.A., Modeling of the bacterial luciferase-flavin mononucleotide complex combining flexible docking with structure-activity data. Protein ScL, 10, 1563, 2001. 

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