Enzyme trimethylamine dehydrogenase

Foumel, A., Gambarelli, S., Guigliarelli, B., More, C., Asso, M., Chouteau, G., Hille, R., and Bertrand, P. 1998. Magnetic interactions between a 4Fe-4S l+ cluster and a flavin mononucleotide radical in the enzyme trimethylamine dehydrogenase a high-field electron paramagnetic resonance study. Journal of Chemical Physics 109 10905-10913. 

The transition flavoquinone-flavosemiquinone seems not to be useful in flavoproteins catalysis. Only trimethylamine dehydrogenase electron-acceptor flavoprotein, isolated from bacterium W3A1 , makes probably use of this shuttle 240,241) -j-jjg enzyme forms a very air-stable anionic flavosemiquinone. 

In contrast to the flavin oxidases, flavin dehydrogenases pass electrons to carriers within electron transport chains and the flavin does not react with 02. Examples include a bacterial trimethylamine dehydrogenase (Fig. 15-9) which contains an iron-sulfur duster that serves as the immediate electron acceptor167 169 and yeast flavocytochrome b2, a lactate dehydrogenase that passes electrons to a built-in heme group which can then pass the electrons to an external acceptor, another heme in cytochrome c.170-173 Like glycolate oxidase, these enzymes bind their flavin coenzyme at the ends of 8-stranded a(i barrels similar... 

C. Loechel, A. Basran, J. Basran, N. S. Scrutton and E. A. Hall, Using trimethylamine dehydrogenase in an enzyme linked amperometric electrode. Part 1. Wild-type enzyme redox mediation, Analyst, 128(2) (2003) 166-172 Part 2. Rational design engineering of a wired mutant, Analyst, 128(7) (2003) 889-898. 

Basran, J., Sutcliffe, M. J., Hille, R., and Scrutton, N. S., 1999a, Reductive half-reaction of the H172Q mutant of trimethylamine dehydrogenase evidence against a carbanion mechanism and assignment of kinetically influential ionizations in the enzyme-substrate complex, Biochem. J. 341 3079314. 

Mewies, M., Packman, L. C., Mathews, F. S., and Scrutton, N. S., 1996, Flavinylation in wild-type trimethylamine dehydrogenase and differentially charged mutant enzymes a study of the protein environment around the N1 of the flavin isoalloxazine, Biochem. J. 317 2679272. 

Mitochondrial succinate dehydrogenase, which catalyzes the reaction of Eq. 15-21, contains a flavin prosthetic group that is covalently attached to a histidine side chain. This modified FAD was isolated and identified as 8a-(AF -histidyl)-FAD. The same prosthetic group has also been found in several other dehy-drogenases. It was the first identified member of a series of modified FAD or riboflavin 5 -phosphate derivatives that are attached by covalent bonds to the active sites of more than 20 different enzymes. These include 8a-(AF -histidyl)-FMN, 8a-(N -histidyl)-FAD, 8a-(0-tyrosyl-FAD), and 6-(S-cysteinyl)-riboflavin 5 -phosphate, which is foxmd in trimethylamine dehydrogenase (Fig. 15-9). " An 8-hydroxy analog of FAD (-OH in place of the 8-CH3)... 

Stopped-flow studies on electron transfer between two-electron reduced trimethylamine dehydrogenase and ETF are complicated by internal electron-transfer steps between the flavin and iron—sulfur center of trimethylamine dehydrogenase " therefore, a modified enzyme in which the FMN prosthetic group was derivatized by phenylhydrazine, making it redox inert, was used." " This modified enzyme, reduced by one electron by dithionite, reacts with oxidized FTF" at 5 °C and pH 7.0 with a bimolecular rate constant of... 

The above schemes work reasonably well for certain enzyme reactions, especially for substrates where oxygen addition/loss occurs at a main group element (e.g., N, S, Se, Cl, see Table I). In addition to SO and nitrate reductase, key examples are DMSOR, trimethylamine oxide reductase, chlorate reductase, and selenate reductase. In the case of enzymes catalyzing C-based redox reactions of organic molecules, notably XDH and aldehyde oxidase, a direct OAT step is unlikely and is replaced by mechanistic steps typical of hydro-xylation (2). The essential features of the mechanism are shown in Fig. 10 for xanthine dehydrogenase/oxidase. 

Enzymes in this family include DMSO reductase, biotin 5-oxide reductase, dissimilatory nitrate reductase, trimethylamine A-oxide reductase, and formate dehydrogenase they are found exclusively in bacteria and fungi and act as terminal respiratory reductases during anaerobic growth in the presence of their respective substrates. " DMSO reductases catalyze the reaction shown in equation (5) the water-soluble enzymes from the purple phototrophic bacteria R. capsula-tus and R. sphaeroides are among the simplest Mo-MPT enzymes, being relatively small (ca. 85 kDa), single subunit... 

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