FMN complexes

FIGURE 5. Stereo close-up view of the interdomain interface of the BMP/FMN complex. Helix C, the H/I loop and the helix K K/L-loop of BMP and the FMN of BM3/FMN are shown in darker lines. The 3l-al helix-loop, N-terminalportion of o2, the P4/a4 and P5/a5 loops of BM3/FMN and the heme of BMP are shown in lighter lines. The locations of 40 water molecules within the interface are shown as dark spheres. 

The components of the respiratory chain contain a variety of redox cofactors. Complex I (NADH-Q reductase > 600 kJDa) contains five iron-sulfur clusters and FMN. Complex II (succinate-Q reductase 150 kDa) contains sev-... 

The comments in the text concerning the tryptophan-FMN complex presumably apply also to this complex. 

Riboflavin, also called vitamin B2, is stmcturally composed of an isoafloxazine ring with a ribityl side chain at the nitrogen at position 10. This vitamin functions metabol-icafly as the essoitial component of two flavin coenzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), complexed with proteins, which act as intmnediaries in transfers of electrons in biological oxidation-reduction reactions. Both FAD and FMN function as coenzymes for flavoproteins of flavoenzymes. Flavoproteins are essoitial for the metabolism of carbohydrates, amino acids, and lipids and for pyridoxine and folate conversion to their respective coenzyme forms. 

As its name implies, this complex transfers a pair of electrons from NADH to coenzyme Q a small, hydrophobic, yellow compound. Another common name for this enzyme complex is NADH dehydrogenase. The complex (with an estimated mass of 850 kD) involves more than 30 polypeptide chains, one molecule of flavin mononucleotide (FMN), and as many as seven Fe-S clusters, together containing a total of 20 to 26 iron atoms (Table 21.2). By virtue of its dependence on FMN, NADH-UQ reductase is a jlavoprotein. 

Three protein complexes have been isolated, including the flavoprotein (FP), iron-sulfur protein (IP), and hydrophobic protein (HP). FP contains three peptides (of mass 51, 24, and 10 kD) and bound FMN and has 2 Fe-S centers (a 2Fe-2S center and a 4Fe-4S center). IP contains six peptides and at least 3 Fe-S centers. HP contains at least seven peptides and one Fe-S center. 

Li, Z., and Meighen, E. A. (1994). The turnover of bacterial luciferase is limited by a slow decomposition of the ternary enzyme-product complex of luciferase, FMN, and fatty acid. J. Biol. Chem. 269 6640-6644. 

Complex 1 850 kDa (probably a dimer in membrane) About 40 1 FMN covalently bound, bound 16-24 Fe-S atoms in 5 to 7 centers Spans membrane, NADH site on matrix face, UQ site in membrane 0.06 UQ Pumps protons out of matrix during electron transporl/2e"... 

All the complexes consist of several subunits (Table 2) complex I has a flavin mononucleotide (FMN) prosthetic group and complex II a flavin adenine dinucleotide (FAD) prosthetic group. Complexes I, II, and III contain iron-sulphur (FeS) centers. These centers contain either two, three, or four Fe atoms linked to the sulphydryl groups of peptide cysteine residues and they also contain acid-labile sulphur atoms. Each center can accept or donate reversibly a single electron. 

A still more complicated reaction is the chemiluminescent oxidation of sodium hydrogen sulfide, cysteine, and gluthathione by oxygen in the presence of heavy metal catalysts, especially copper ions 60>. When copper is used in the form of the tetrammin complex Cu(NH3) +, the chemiluminescence is due to excited-singlet oxygen when the catalyst is copper flavin mononucleotide (Cu—FMN), additional emission occurs from excited flavin mononucleotide. From absorption spectroscopic measurements J. Stauff and F. Nimmerfall60> concluded that the first reaction step consists in the addition of oxygen to the copper complex ... 

Such a process is supposed to occur within the limits of Q-cycle mechanism (Figure 23.2). In accord with this scheme ubihydroquinone reduced dioxygen in Complex III, while superoxide producers in Complex I could be FMN or the FeS center [12]. Zhang et al. [24] also suggested that the Q-cycle mechanism is responsible for the superoxide production by the succinate-cytochrome c reductase in bovine heart mitochondria and that FAD of succinate dehydrogenase is another producer of superoxide. Young et al. [25] concluded that, in addition to Complex III, flavin-containing enzymes and FeS centers are also the sites of superoxide production in liver mitochondria. 

NADH-coenzyme Q (CoQ) oxidoreductase, transfers electrons stepwise from NADH, through a flavoprotein (containing FMN as cofactor) to a series of iron-sulfur clusters (which will be discussed in Chapter 13) and ultimately to CoQ, a lipid-soluble quinone, which transfers its electrons to Complex III. A If, for the couple NADH/CoQ is 0.36 V, corresponding to a AG° of —69.5 kJ/mol and in the process of electron transfer, protons are exported into the intermembrane space (between the mitochondrial inner and outer membranes). 

Key I complex I contains FMN and Fe-S accepts electrons and H+from NADH... 

The report of Basran et al. (entry 5 of Table 2) contains two studies involving hydride transfer with nicotinamide cofactors. In morphinone-reductase catalyzed reduction by NADH of the flavin cofactor FMN (schematic mechanism in Fig. 5), the primary isotope effects are modest (around 4 for H/D), but exhibit a small value of Ajj/Aq (0.13) and an exalted isotopic difference in energies of activation (8.2kJ/mol) that alone would have generated an isotope effect around 30. The enthalpies of activation are in the range of 35-45 kJ/mol. This is behavior typical of Bell tunneling as discussed above. It can also be reproduced by more complex models, as will be discussed in later parts of this review. 

Albracht SPJ, Hedderich R. 2000. Learning from hydrogenases location of a proton pump and of a second FMN in bovine NADH ubiquinone oxidoreductase (complex I) FEBS Lett 485 1-6. 

Fig. 12. Crystal structure of the complex formed between the heme and FMN domains of cytochrome P450BM-3 133). The FMN domain docks on the proximal surface of the heme domain. The thicker trace in the heme domain highlights residues 387 to the heme ligand, Cys400. This section of polypeptide contacts the FMN and might provide an electron transfer conduit to the heme ligand. The two interacting surfaces are electrostatically complementary, with similar complementarity expected for HO and NOS.

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