Dehydrogenases trimethylamine dehydrogenase

Lim, L.W., et al. Three-dimensional structure of the iron-sulfur flavoprotein trimethylamine dehydrogenase at 2.4 A resolution. J. Biol. Chem. 261 15140-15146, 1986. 

Like PDR, trimethylamine dehydrogenase (TMADH) from Methylo-philus methylotrophus W3A1 provides an example of a system in which an iron-sulfur center, in this case a [4Fe-4S] cluster, interacts... 

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. 

R. Hille and R.F. Anderson, Coupled electron/proton transfer in complex flavoproteins — solvent kinetic isotope effect studies of electron transfer in xanthine oxidase and trimethylamine dehydrogenase. J. Biol. Chem. 276, 31193-31201 (2001). 

There is, up to now, one exception known to the four kinds of the above mentioned covalent linkages. The prosthetic group of trimethylamine dehydrogenase is linked via the C(6)-atom of the flavin to a cysteinyl residue (Scheme 3, (5)). As mentioned above the less reactivity of C(6) of flavin as compared to that of CH3(8) requires probably some chemical modification of the prosthetic by biologicai means prior to covalent attachment. The C(6)-S-Cysteinyl flavin was synthesized recently starting with 6-nitro flavin which was subsequently reduced to the amino derivative and transformed to the corresponding bromo derivative via diazotation. Reaction of the bromo derivative with cysteine gave the desired 6-S-Cysteinyl derivative... 

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. 

The properties of the semiquinone from of the ETF isolated from the methylotrophic bacterium resemble those of the bacterial flavodoxins with the exception that flavodoxins form neutral semiquinones whereas this ETF forms an anionic semiquinone. Nearly quantitative anionic semiquinone formation is observed either in the presence of excess dithionite or when excess trimethylamine and a catalytic amount of trimethylamine dehydrogenase are added. Of interest is the apparent stability of the anionic semiquinone towards oxidation by O2 but not to oxidizing agents such as ferricyanide. This appears to be the first example of an air-stable protein-bound anionic flavin semiquinone. Future studies on the factors involved in imparting this resistance to O2 oxidation by the apoprotein are looked forward to with great interest. 

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... 

These include 8a-(Ne2-histidyl)-FMN,221 8a-(N81-histidyl)-FA D,222 8a-(0-tyrosyl-FAD),223 and 6-(S-cysteinyl)-riboflavin 5 -phosphate, which is found in trimethylamine dehydrogenase (Fig. 15-9).224 An 8-hydroxy analog of FAD (-OH in place of the 8-CH3)... 

Measurements of many kinds have been made between natural donor-acceptor pairs such as cytochrome c-cytochrome (y,161462 cytochrome c-cytochrome c peroxidase (Fig. 16-9),153163-166 trimethylamine dehy-drogenase-FMN to Fe4S4 center (Fig. 15-9),167 and methylamine dehydrogenase (TTQ radical)-amicya-nin (Cu2+).168 Designed metalloproteins are being studied as well.169 Femtosecond laser spectroscopy is providing a new approach.169,3... 

Iron-sulfur clusters are found in flavoproteins such as NADH dehydrogenase (Chapter 18) and trimethylamine dehydrogenase (Fig. 15-9) and in the siroheme-containing sulfite reductases and nitrite reductases.312 These two reductases are found both in bacteria and in green plants. 

A number of other reductases and dehydrogenases, including dissimilatory nitrate reductases of E. coli and of denitrifying bacteria (Chapter 18), belong to the DMSO reductase family. Other members are reductases for biotin S-oxide,649 trimethylamine N-oxide, and polysulfides as well as formate dehydrogenases (Eq. 16-63), formylmethanofuran dehydrogenase (Fig. 15-22,... 

Trimethylamine dehydrogenase 782, 784s Trimethylarsonium lactic acid, 387s Trimethyllysine... 

A molybdenum cofactor has been isolated from Proteus mirabilis 047, and has a molecular weight greater than 1000. The molybdoenzymes of E. coli, in addition to the formate dehydrogenases described above and the nitrate reductase (Section 62.1.9.6), also include the membrane-bound trimethylamine oxidase1044 and the soluble biotin sulfoxide reductase.1045... 

Loechel et al. [20] Trimethylamine Fish Trimethylamine dehydrogenase (TMADH) (Dimethylamine) methylene ferrocene (DMAMFe)... 

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. 

A barrels nearly circular small helix between /7-strand 8 and a-helix 8 domain covering N-terminus of the barrel glycolate oxidase, trimethylamine dehydrogenase... 

Oxidases 22 23 24 25 26 27 28 29 30 + Alcohol dehydrogenase, class 1, ADH2 (B) (125) + Alcohol dehydrogenase, class 1, ADH3 () (126) + Aldehyde dehydrogenase, mitochondrial (127) + Monoamine oxidase A (128) + Monoamine oxidase B (129) + Catalase (130) + Superoxide dismutase (131) + Trimethylamine TV-oxidase (132) + Dihydropyrimidine dehydrogenase (133)... 

Baskakov, I., A. Wang, and D.W. Bolen (1998). Trimethylamine-N-oxide counteracts urea effects on rabbit muscle lactate dehydrogenase function A test of the counteraction hypothesis. Biophys. J. 74 2666-2673. 

---