DB code: T00015

CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
3.40.50.720 : Rossmann fold
3.50.50.60 : FAD/NAD(P)-binding domain
E.C. 1.5.8.2
CSA 2tmd
M-CSA 2tmd
MACiE M0114

CATH domain Related DB codes (homologues)
3.20.20.70 : TIM Barrel S00215 S00217 S00218 S00219 S00532 S00198 S00220 S00745 S00537 S00538 S00539 S00826 S00841 S00235 S00239 S00240 S00243 S00244 S00199 S00200 S00201 S00221 S00222 S00847 S00224 S00225 S00226 D00014 D00029 M00141 T00239 D00664 D00665 D00804 D00863 T00089
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00610 S00625 S00319 S00328 S00329 S00330 S00331 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00336 S00334 T00219 S00339 D00513 D00001 D00002 D00003 D00005 D00007 D00008 D00010 D00012 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00002 T00010 T00011 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109
3.50.50.60 : FAD/NAD(P)-binding domain M00163 D00015 D00041 D00042 D00045 D00064 D00071 T00004 T00017 T00025 T00211 T00213 T00233 T00242

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P16099 Trimethylamine dehydrogenase
TMADh
EC 1.5.8.2
PF00724 (Oxidored_FMN)
PF07992 (Pyr_redox_2)
[Graphical View]

KEGG enzyme name
trimethylamine dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P16099 DHTM_METME Trimethylamine + H(2)O + electron-transferring flavoprotein = dimethylamine + formaldehyde + reduced electron- transferring flavoprotein. Homodimer. Binds 1 FMN covalently per subunit. Binds 1 4Fe-4S cluster per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00680 Methane metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id L00024 C00061 C00565 C00001 C04253 C00543 C00067 C04570
E.C.
Compound [4Fe-4S] FMN Trimethylamine H2O Electron-transferring flavoprotein Dimethylamine Formaldehyde Reduced electron-transferring flavoprotein
Type heavy metal,sulfide group amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ion amine group H2O amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,peptide/protein,phosphate group/phosphate ion amine group carbohydrate amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,peptide/protein,phosphate group/phosphate ion
ChEBI 33725
 33725
 		17621
 17621
 		18139
 18139
 		15377
 15377
 		17170
 17170
 		16842
 16842
PubChem 643976
 643976
 		1146
 1146
 		22247451
 962
 22247451
 962
 		674
 674
 		712
 712
1djnA01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1djnB01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1djqA01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1djqB01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1o94A01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1o94B01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1o95A01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1o95B01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
2tmdA01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
2tmdB01 Bound:SF4 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1djnA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1djnB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1djqA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1djqB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1o94A02 Unbound Unbound Unbound Bound:AMP (chain C) Unbound Unbound Unbound
1o94B02 Unbound Unbound Unbound Bound:AMP (chain E) Unbound Unbound Unbound
1o95A02 Unbound Unbound Unbound Bound:AMP (chain E) Unbound Unbound Unbound
1o95B02 Unbound Unbound Unbound Bound:AMP (chain C) Unbound Unbound Unbound
2tmdA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2tmdB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1djnA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1djnB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1djqA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1djqB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1o94A03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1o94B03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1o95A03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1o95B03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2tmdA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2tmdB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P16099 & literature [20], [31]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1djnA01 TYR 60;TYR 169;HIS 172;ASP 267 CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
1djnB01 TYR 60;TYR 169;HIS 172;ASP 267 CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
1djqA01 TYR 60;TYR 169;HIS 172;ASP 267 ;CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding) mutant C30A
1djqB01 TYR 60;TYR 169;HIS 172;ASP 267 ;CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding) mutant C30A
1o94A01 TYR 60;TYR 169;HIS 172;ASP 267 CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
1o94B01 TYR 60;TYR 169;HIS 172;ASP 267 CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
1o95A01 TYR 60;TYR 169;HIS 172;ASP 267 CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
1o95B01 TYR 60;TYR 169;HIS 172;ASP 267 CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
2tmdA01 TYR 60;TYR 169;HIS 172;ASP 267 CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
2tmdB01 TYR 60;TYR 169;HIS 172;ASP 267 CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
1djnA02
1djnB02
1djqA02
1djqB02
1o94A02
1o94B02
1o95A02
1o95B02
2tmdA02
2tmdB02
1djnA03
1djnB03
1djqA03
1djqB03
1o94A03
1o94B03
1o95A03
1o95B03
2tmdA03
2tmdB03

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[11]
SCHEME 1, p.30875-30878
[12]
FIG. 10, p.13949-13950
[14]
[18]
Fig.7, p.46-48
[20]
Scheme 3, p.772-778
[21]
[22]
Scheme 1
[23]
p.13160-13161
[24]
SCHEME 1, p.13152-13153
[25]
[29]
Fig.1
[30]
Fig.2
[31]
Fig.1, p.42892
[34]
Fig.4
[35]
[36]
p.221-223

References
[1]
Resource
Comments
Medline ID
PubMed ID 6297456
Journal Biochem J
Year 1982
Volume 207
Pages 241-52
Authors Steenkamp DJ, Beinert H
Title Mechanistic studies on the dehydrogenases of methylotrophic bacteria. 2. Kinetic studies on the intramolecular electron transfer in trimethylamine and dimethylamine dehydrogenase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 6297455
Journal Biochem J
Year 1982
Volume 207
Pages 233-9
Authors Steenkamp DJ, Beinert H
Title Mechanistic studies on the dehydrogenases of methylotrophic bacteria. 1. The influence of substrate binding to reduced trimethylamine dehydrogenase on the intramolecular electron transfer between its prosthetic groups.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7169636
Journal J Mol Biol
Year 1982
Volume 162
Pages 869-76
Authors Lim LW, Mathews FS, Steenkamp DJ
Title Crystallographic study of the iron-sulfur flavoprotein trimethylamine dehydrogenase from the bacterium W3A1.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 6501301
Journal J Biol Chem
Year 1984
Volume 259
Pages 14458-62
Authors Lim LW, Shamala N, Mathews FS, Steenkamp DJ
Title Molecular structure of trimethylamine dehydrogenase from the bacterium W3A1 at 6.0-A resolution.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 3002478
Journal Biochim Biophys Acta
Year 1986
Volume 869
Pages 81-8
Authors Stevenson RC, Dunham WR, Sands RH, Singer TP, Beinert H
Title Studies on the spin-spin interaction between flavin and iron-sulfur cluster in an iron-sulfur flavoprotein.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 3771568
Journal J Biol Chem
Year 1986
Volume 261
Pages 15140-6
Authors Lim LW, Shamala N, Mathews FS, Steenkamp DJ, Hamlin R, Xuong NH
Title Three-dimensional structure of the iron-sulfur flavoprotein trimethylamine dehydrogenase at 2.4-A resolution.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 2545689
Journal J Biol Chem
Year 1989
Volume 264
Pages 11887-92
Authors Bellamy HD, Lim LW, Mathews FS, Dunham WR
Title Studies of crystalline trimethylamine dehydrogenase in three oxidation states and in the presence of substrate and inhibitor.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 1917829
Journal J Bacteriol
Year 1991
Volume 173
Pages 5935-43
Authors Sambasivarao D, Weiner JH
Title Dimethyl sulfoxide reductase of Escherichia coli: an investigation of function and assembly by use of in vivo complementation.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 1651321
Journal J Biol Chem
Year 1991
Volume 266
Pages 15244-52
Authors Rohlfs RJ, Hille R
Title Intramolecular electron transfer in trimethylamine dehydrogenase from bacterium W3A1.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), AND PARTIAL SEQUENCE
Medline ID 92202205
PubMed ID 1551870
Journal J Biol Chem
Year 1992
Volume 267
Pages 6611-9
Authors Barber MJ, Neame PJ, Lim LW, White S, Matthews FS
Title Correlation of x-ray deduced and experimental amino acid sequences of trimethylamine dehydrogenase.
Related PDB 2tmd
Related UniProtKB P16099
[11]
Resource
Comments
Medline ID
PubMed ID 7983019
Journal J Biol Chem
Year 1994
Volume 269
Pages 30869-79
Authors Rohlfs RJ, Hille R
Title The reaction of trimethylamine dehydrogenase with diethylmethylamine.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8188674
Journal J Biol Chem
Year 1994
Volume 269
Pages 13942-50
Authors Scrutton NS, Packman LC, Mathews FS, Rohlfs RJ, Hille R
Title Assembly of redox centers in the trimethylamine dehydrogenase of bacterium W3A1. Properties of the wild-type enzyme and a C30A mutant expressed from a cloned gene in Escherichia coli.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 7849604
Journal Protein Sci
Year 1994
Volume 3
Pages 1889-92
Authors Raine AR, Scrutton NS, Mathews FS
Title On the evolution of alternate core packing in eightfold beta/alpha-barrels.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 7673198
Journal J Biol Chem
Year 1995
Volume 270
Pages 22196-207
Authors Rohlfs RJ, Huang L, Hille R
Title Prototropic control of intramolecular electron transfer in trimethylamine dehydrogenase.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8810917
Journal Biochemistry
Year 1996
Volume 35
Pages 12111-8
Authors Falzon L, Davidson VL
Title Intramolecular electron transfer in trimethylamine dehydrogenase: a thermodynamic analysis.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8652588
Journal Biochemistry
Year 1996
Volume 35
Pages 2445-52
Authors Falzon L, Davidson VL
Title Kinetic model for the regulation by substrate of intramolecular electron transfer in trimethylamine dehydrogenase.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 8662829
Journal J Biol Chem
Year 1996
Volume 271
Pages 13401-6
Authors Huang L, Scrutton NS, Hille R
Title Reaction of the C30A mutant of trimethylamine dehydrogenase with diethylmethylamine.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 8993316
Journal Biochemistry
Year 1997
Volume 36
Pages 41-8
Authors Wilson EK, Huang L, Sutcliffe MJ, Mathews FS, Hille R, Scrutton NS
Title An exposed tyrosine on the surface of trimethylamine dehydrogenase facilitates electron transfer to electron transferring flavoprotein: kinetics of transfer in wild-type and mutant complexes.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9725623
Journal Protein Eng
Year 1998
Volume 11
Pages 447-55
Authors Ertughrul OW, Errington N, Raza S, Sutcliffe MJ, Rowe AJ, Scrutton NS
Title Probing the stabilizing role of C-terminal residues in trimethylamine dehydrogenase.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10830100
Journal Biochem Soc Trans
Year 1999
Volume 27
Pages 767-79
Authors Scrutton NS
Title Colworth Medal Lecture. Enzymes in the quantum world.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10093733
Journal Biochem Soc Trans
Year 1999
Volume 27
Pages 196-201
Authors Scrutton NS, Basran J, Wilson EK, Chohan KK, Jang MH, Sutcliffe MJ, Hille R
Title Electron transfer in trimethylamine dehydrogenase and electron-transferring flavoprotein.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10555975
Journal Biochemistry
Year 1999
Volume 38
Pages 14927-40
Authors Roberts P, Basran J, Wilson EK, Hille R, Scrutton NS
Title Redox cycles in trimethylamine dehydrogenase and mechanism of substrate inhibition.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 10224070
Journal J Biol Chem
Year 1999
Volume 274
Pages 13155-61
Authors Basran J, Jang MH, Sutcliffe MJ, Hille R, Scrutton NS
Title The role of Tyr-169 of trimethylamine dehydrogenase in substrate oxidation and magnetic interaction between FMN cofactor and the 4Fe/4S center.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 10224069
Journal J Biol Chem
Year 1999
Volume 274
Pages 13147-54
Authors Jang MH, Basran J, Scrutton NS, Hille R
Title The reaction of trimethylamine dehydrogenase with trimethylamine.
Related PDB
Related UniProtKB
[25]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10869173
Journal Biochemistry
Year 2000
Volume 39
Pages 7678-88
Authors Trickey P, Basran J, Lian LY, Chen Z, Barton JD, Sutcliffe MJ, Scrutton NS, Mathews FS
Title Structural and biochemical characterization of recombinant wild type and a C30A mutant of trimethylamine dehydrogenase from methylophilus methylotrophus (sp. W(3)A(1)).
Related PDB 1djn 1djq
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10859304
Journal J Biol Chem
Year 2000
Volume 275
Pages 30781-6
Authors Anderson RF, Jang MH, Hille R
Title Radiolytic studies of trimethylamine dehydrogenase. Spectral deconvolution of the neutral and anionic flavin semiquinone, and determination of rate constants for electron transfer in the one-electron reduced enzyme.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 10777543
Journal J Biol Chem
Year 2000
Volume 275
Pages 12546-52
Authors Jang MH, Scrutton NS, Hille R
Title Formation of W(3)A(1) electron-transferring flavoprotein (ETF) hydroquinone in the trimethylamine dehydrogenase x ETF protein complex.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 10766748
Journal J Biol Chem
Year 2000
Volume 275
Pages 21349-54
Authors Jones M, Basran J, Sutcliffe MJ, Gunter Grossmann J, Scrutton NS
Title X-ray scattering studies of Methylophilus methylotrophus (sp. W3A1) electron-transferring flavoprotein. Evidence for multiple conformational states and an induced fit mechanism for assembly with trimethylamine dehydrogenase.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 10694883
Journal Trends Biochem Sci
Year 2000
Volume 25
Pages 126-32
Authors Fraaije MW, Mattevi A
Title Flavoenzymes: diverse catalysts with recurrent features.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 11304539
Journal J Biol Chem
Year 2001
Volume 276
Pages 24581-7
Authors Basran J, Sutcliffe MJ, Scrutton NS
Title Deuterium isotope effects during carbon-hydrogen bond cleavage by trimethylamine dehydrogenase. Implications for mechanism and vibrationally assisted hydrogen tunneling in wild-type and mutant enzymes.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 11553643
Journal J Biol Chem
Year 2001
Volume 276
Pages 42887-92
Authors Basran J, Sutcliffe MJ, Scrutton NS
Title Optimizing the Michaelis complex of trimethylamine dehydrogenase: identification of interactions that perturb the ionization of substrate and facilitate catalysis with trimethylamine base.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 11429403
Journal J Biol Chem
Year 2001
Volume 276
Pages 34142-7
Authors Chohan KK, Jones M, Grossmann JG, Frerman FE, Scrutton NS, Sutcliffe MJ
Title Protein dynamics enhance electronic coupling in electron transfer complexes.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 11336819
Journal Trends Microbiol
Year 2001
Volume 9
Pages 196-8
Authors Sargent F
Title A marriage of bacteriology with cell biology results in twin arginines.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 12084049
Journal Eur J Biochem
Year 2002
Volume 269
Pages 3096-102
Authors Sutcliffe MJ, Scrutton NS
Title A new conceptual framework for enzyme catalysis. Hydrogen tunnelling coupled to enzyme dynamics in flavoprotein and quinoprotein enzymes.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 11756429
Journal J Biol Chem
Year 2002
Volume 277
Pages 8457-65
Authors Jones M, Talfournier F, Bobrov A, Grossmann JG, Vekshin N, Sutcliffe MJ, Scrutton NS
Title Electron transfer and conformational change in complexes of trimethylamine dehydrogenase and electron transferring flavoprotein.
Related PDB
Related UniProtKB
[36]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12567183
Journal Nat Struct Biol
Year 2003
Volume 10
Pages 219-25
Authors Leys D, Basran J, Talfournier F, Sutcliffe MJ, Scrutton NS
Title Extensive conformational sampling in a ternary electron transfer complex.
Related PDB 1o94 1o95
Related UniProtKB

Comments
This enzyme was transferred from E.C. 1.5.99.7 to E.C. 1.5.8.2.
According to the literature [11] & [20], this enzyme catalyzes the following reactions.
(A) Hydride transfer from substrate (trimethylamine) to FMN.
(B) Electron transfer from FMN to 4Fe-4S.
(C) Exchange of double-bonded atoms (Schiff-base deformation by water).
(D) Electron transfer from the reduced 4Fe-4S to flavin group of electron-transferring flavoprotein (ETF).
According to the literature [20], the reductive half-reaction consists the reactions (A) and (B), whereas the oxidative half-reaction consists the reaction (D).

Created Updated
2004-12-16 2009-02-26