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Last modified: 11 November 1998

Trimethylamine dehydrogenase family
Prosthetic group Formal oxidation states
Fe4S4 image
[Fe4S4](SgammaCys)4
[Fe4S4]+; [Fe4S4]2+
FMN image
FMN(SgammaCys)
FMN; FMN· (semiquinone); FMNH2

Trimethylamine dehydrogenase (TMADH; EC 1.5.99.7) isolated from the methylotrophic bacterium W3A1 is a homodimer, with each subunit containing a covalently bound 6­cysteinyl FMN coenzyme and a [Fe4S4] (ferredoxin­type) centre [1, 2]. TMADH also possesses 1 equivalent of tightly bound ADP per monomer, the function of which remains unknown [3]. The enzyme catalyses the oxidative demethylation of trimethylamine to dimethylamine and formaldehyde, passing the pair of reducing equivalents thus obtained individually to its physiological oxidant, an electron­transferring flavoprotein (ETF) [2 and references therein].

The 3­D structure of TMADH has been determined [4] (see Figure 2TMD). Each monomer is folded into three structural domains (Figure 2TMD b). The largest domain (I), at the N­terminus of the molecule, is folded as an eight­stranded parallel alpha/ß barrel. It contains the [Fe4S4] and covalently bound FMN cofactors separated by about 4 Å. The other two domains (II and III) have the ßalphaß topologies typical of pyridine dinucleotide­binding folds; one of these domains binds ADP [4].

TMADH family in enzyme databases

ENZYME LIGAND BRENDA Official name Alternative name
1.5.99.7 1.5.99.7 1.5.99.7 Trimethylamine dehydrogenase TMADH
1.5.99.10 1.5.99.10
-
 Dimethylamine dehydrogenase DMADH
1.3.1.31 1.3.1.31 1.3.1.31 2­enoate reductase Enoate reductase
1.3.1.34 1.3.1.34 1.3.1.34 2,4­dienoyl­CoA reductase (NADPH) 4­enoyl­CoA reductase (NADPH)

TMADH family in SWISS­PROT/TREMBL

P16099 DHTM_METME Trimethylamine dehydrogenase (EC 1.5.99.7) (TMADH); Methylotrophus methylophilus (bacterium W3A1)
P19410 BAIC_EUBSP Bile acid­inducible operon protein C (BaiC); Eubacterium sp. (strain VPI 12708)
P32370 BAIH_EUBSP NADH­dependent flavin oxidoreductase (EC 1.-.-.-) (BaiH); Eubacterium sp. (strain VPI 12708)
P42593 FADH_ECOLI 2,4­dienoyl­CoA reductase (EC 1.3.1.34) (fadH); Escherichia coli
P32382 NADO_THEBR NADH oxidase (EC 1.-.-.-); Thermoanaerobacter brockii (Thermoanaerobium brockii)
P54550 YQJM_BACSU Probable NADH­dependent flavin oxidoreductase (EC 1.-.-.-) (YqjM); Bacillus subtilis
Q48303 DHDM_HYPSX Dimethylamine dehydrogenase; Hyphomicrobium sp.
Q48962 Q48962 Similar to trimethylamine dehydrogenase (fragment); Mycoplasma capricolum
O29794 O29794 NADH oxidase (NOXB-1); Archaeoglobus fulgidus
O29006 O29006 NADH oxidase (NOXB-2); Archaeoglobus fulgidus
O29991 O29991 NADH­dependent flavin oxidoreductase; Archaeoglobus fulgidus
O50431 O50431 2,4­dienoyl­CoA reductase (EC 1.3.1.34) (fadH); Mycobacterium tuberculosis
O52922 O52922 2­Enoate reductase (EC 1.3.1.31) (fragment); Clostridium kluyveri
O52933 O52933 2­Enoate reductase (EC 1.3.1.31); Clostridium tyrobutyricum
O52935 O52935 2­Enoate reductase (EC 1.3.1.31) (fragment); Moorella thermoacetica

TMADH family in alignment databases

Protein Family Pfam LPFC 3­D alignment
08904; (trimethylamine dehydrogenase)
-
-

TMADH family in 3­D databases

Trimethylamine dehydrogenase contains a single cubane­like [Fe4S4] cluster and an FMN molecule per monomer (see Figure 2TMD).

PDB scop BSMRELI
Base		 Header
2tmd 2tmd 2tmd 2tmd Trimethylamine dehydrogenase (complex with ADP); Methylotrophus methylophilus (bacterium W3A1)

References

  1. Kasprzak, A.A., Papas, E.J. and Steenkamp, D.J. (1983) Identity of the subunits and the stoicheiometry of prosthetic groups in trimethylamine dehydrogenase and dimethylamine dehydrogenase. Biochem. J. 211, 535-541.
  2. Huang, L., Rohlfs, R.J. and Hille, R. (1995) The reaction of trimethylamine dehydrogenase with electron transferring flavoprotein. J. Biol. Chem. 270, 23958-23965.
  3. Lim, L.W., Mathews, F.S. and Steenkamp, D.J. (1988) Identification of ADP in the iron-sulfur flavoprotein trimethylamine dehydrogenase. J. Biol. Chem. 263, 3075-3078.
  4. Lim, L.W., Shamala, N., Mathews, F.S., Steenkamp, D.J., Hamlin, R. and Xuong, N.H. (1986) Three­dimensional structure of the iron-sulfur flavoprotein trimethylamine dehydrogenase at 2.4­Å resolution. J. Biol. Chem. 261, 15140-15146.
Bibliography on structural studies of trimethylamine dehydrogenase