Structure flavin mononucleotide

The first structure, flavodoxin (Figure 4.14a), has one such position, between strands 1 and 3. The connection from strand 1 goes to the right and that from strand 3 to the left. In the schematic diagram in Figure 4.14a we can see that the corresponding a helices are on opposite sides of the p sheet. The loops from these two p strands, 1 and 3, to their respective a helices form the major part of the binding cleft for the coenzyme FMN (flavin mononucleotide). 

Riboflavin, or vitamin B2, is a constituent and precursor of both riboflavin 5 -phosphate, also known as flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD). The name riboflavin is a synthesis of the names for the molecule s component parts, ribitol and flavin. The structures of riboflavin. 

Vitamin B2. Figure 2 Structure of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). 

FIGURE 10.1 The structural formula of riboflavin and partial structures of riboflavin compounds. The latter show only those portions of the molecule that differ from riboflavin. 1 — Riboflavin (RF), 2 — flavin mononucleotide or 5 -riboflavin monophosphate (FMN or 5 -FMN), 3 — flavin adenine dinucleotide (FAD). 

The second type of biological electron transfer involves a variety of small molecules, both organic and inorganic. Examples of these are (a) nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) as two electron carriers and (b) quinones and flavin mononucleotide (FMN), which may transfer one or two electrons. The structure of NAD and its reduced counterpart NADH are shown in Figure 1.12. 

The principles of ESR spectroscopy are very similar to NMR spectroscopy but the technique gives information about electron delocalizations rather than molecular structure and it enables the study of electron transfer reactions and the formation of paramagnetic intermediates in such reactions. In some situations, information regarding molecular structure can be obtained when suitable prosthetic groups are part of a molecule, e.g. FMN (flavin mononucleotide) in certain enzymes or the haem group in haemoglobin. Sometimes it is possible to attach suitable groups to molecules to enable their reactions to be monitored by ESR techniques. Such spin labels as they are called, are usually nitroxide radicals of the type... 

Flavin adenine diphosphate (FAD, flavin adenine dinucleotide) and riboflavin 5 -monophosphate (FMN, flavin mononucleotide), whose structures are shown in Fig. 15-7, are perhaps the most versatile of all... 

Riboflavin has been shown to be a constituent of 2 coenzymes (1) Flavin mononucleotide (FMN) and (2) flavin adenine dinucleotide (FAD). The structures are ... 

In 1989, BH4 was found to be a cofactor for nitric oxide synthase (NOS) [ 126, 127]. BH4 is also involved in dimerization of NOS, as NOS is catalytically active in a homodimer structure. Three isoforms of NOS exist neuronal NOS (NOS 1), inducible NOS (NOS 2) and endothelial NOS (NOS 3). BH4 is essential for all NOS isoforms. The NOS isoforms share approximately 50-60% sequence homology. Each NOS polypeptide is comprised of oxygenase and reductase domains. An N-terminal oxygenase domain contains iron protoporphyrin IX (heme), BH4 and an arginine binding site, and a C-terminal reductase domain contains flavin mononucleotide (FMN), and a reduced nicotin-amide adenine dinucleotide phosphate (NADPH) binding site. 

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. 

Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) are also carriers of electrons and have related chemical structures (Fig. 5). Both of these coenzymes consist of a flavine mononucleotide unit which contains the reactive... 

Oxidation of NADH begins with complex I, also termed NADH dehydrogenase or NADH ubiquinone oxidoreductase. It contains 25 polypeptide chains, flavine mononucleotide (FMN), and several iron-sulfur centers. The function of this complex is to reduce a substance called ubiquinone (UQ or CoQ), whose structure is shown in Figure 17.5. UQ is not protein bound and can move about freely. In the process of reducing UQ, the NADH is oxidized to NAD+. It is now accepted that in complex I, NADH first reduces FMN, and the resulting FMNH2 then transfers its electrons through at least three iron-sulfur centers to UQ. As the electrons pass from NADH to UQ, two to four protons are extruded from the mitochondrial matrix across the inner membrane. 

The oxidizing agents here are related to FAD. We said little about FADH2 as a reducing agent earlier in this chapter because it is rather similar to NADH which we have discussed in detail. FAD is another dinucleotide and it contains an AMP unit linked through the 5 position by a pyrophosphate group to another nucleotide. The difference is that the other nucleotide is flavin mononucleotide. Here is the complete structure. 

The whole thing is FAD. Cutting FAD in half down the middle of the pyrophosphate link would give us two nucleotides, AMP and FMN (flavin mononucleotide). The sugar in each case is ribose (in its furanose form in AMP but in open-chain form in FMN) so the flavin nucleoside is riboflavin. We can abbreviate this complex structure to the reactive part, which is the flavin. The rest we shall just call R ... 

Figure 16-8. Structure and labeling of the isoalloxazine ring and related flavins. Isoalloxazine (benzo[g]pteridine-2,4(3H,10H)-dione) R = R = H. FMN (Flavin mononucleotide) R = CH3 R = CH2- (CH0H)3-CH20-P0f-...

Once the hexameric structure of the yeast FAS was established, the number of functional active sites still remained to be determined. Earlier studies had shown that the functional complex contains approximately six equivalents each of two prosthetic groups 4 -phosphopantetheine [60,63], necessary for the AGP functionality, and flavin mononucleotide [64], an essential component of the enoyl reductase activity. These studies provided an early indication that each of the six active sites in the complex has a full set of the chemical groups necessary for fatty acid synthesis. Nevertheless, conflicting reports appeared in the literature as to the competence of six active sites. Whereas some reports suggested the possibility of half-sites reactivity (only three of the six sites are catalytically competent) [65, 66], others proposed that all six active sites could synthesize fatty acids [62]. Subsequent active site titration experiments were performed which quantitated the amount of fatty acyl products formed in the absence of turnover [67]. Single-turnover conditions were achieved through the use of... 

Enzymatic cofactors, such as nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (EAD), flavin mononucleotide (EMN), and pyridoxal phosphate, are fluorescent and commonly found associated with various proteins where they are responsible for electron transport (see Fig. lb and Table 1). NADH and NADPH in the oxidized form are nonfluorescent, whereas conversely the flavins, FAD and EMN, are fluorescent only in the oxidized form. Both NADH and FAD fluorescence is quenched by the adenine found within their cofactor structures, whereas NADH-based cofactors generally remain fluorescent when interacting with protein structures. The fluorescence of these cofactors is often used to study the cofactors interaction with proteins as well as with related enzymatic kinetics (1, 9-12). However, their complex fluorescent characteristics have not led to widespread applications beyond their own intrinsic function. 

Figure 14.14. Structure of the Oxidized Form of Flaviu Adeuiue Diuucleotide (FAD). This electron carrier consists of a flavin mononucleotide (FMN) unit (shown in blue) and an AMP unit (shown in hlack).

Fig 1. Structure of the flavocytochrome prosthetic groups—protoheme IX and flavin mononucleotide. 

In 1915, Harden and Norris observed that dried yeast, when mixed with lactic acid, reduced methylene blue and formed pyruvic acid 4). Thirteen years later Bernheim prepared an extract from acetone-dried baker s yeast, which had lactate dehydrogenase activity (5). Bach and co-workers demonstrated that the lactate dehydrogenase activity was associated with a 6-type cytochrome, which they named cytochrome 62 (6). In 1954, the enzyme was crystallized, enabling the preparation of pure material and the identification of flavin mononucleotide as a second prosthetic group (2). Since then, significant advances have been made in the analysis of the structure and function of the enzyme. Much of the earlier work on flavocytochrome 62 has already been summarized in previous review articles (7-10). In this article we shall describe recent developments in the study of this enzyme, ranging fi om kinetic, spectroscopic, and structural data to the impact of recombinant DNA technology. 

Fig. 3. The three-dimensional structure of Saccharomyces cerevisiae flavocytochrome 62 as determined by Xia and Mathews (25). (A) The C-terminal tails and flavin mononucleotide (FMN) and heme prosthetic groups are highlighted in this view, which is looking down the fourfold axis of symmetry. The four subunits are numbered 1 to 4 the shaded portions seen in the subunits labeled 2 and 4 represent the two heme domains, which are disordered in the structure. (B) A side view, perpendicular to view A, is also shown. 

Fig. 5. Schematic representation of the structure of a flavocytochrome 62 subunit. A, The heme domain B, the flavodehydrogenase domain C, the C-terminal tail D, the hinge region linking the two domains E, the proteolytically sensitive loop F, flavin mononucleotide G, protoheme IX.

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