EzCatDB: T00015

DB codeT00015
CATH domainDomain 13.20.20.70Catalytic domain
Domain 23.40.50.720
Domain 33.50.50.60
E.C.1.5.8.2
CSA2tmd
MACiEM0114

CATH domainRelated DB codes (homologues)
3.20.20.70S00215,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
3.40.50.720S00543,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
3.50.50.60M00163,D00015,D00041,D00042,D00045,D00064,D00071,T00004,T00017,T00025,T00211,T00213,T00233,T00242

Enzyme Name
Swiss-protKEGG

P16099
Protein nameTrimethylamine dehydrogenasetrimethylamine dehydrogenase
SynonymsTMADh
EC 1.5.8.2

KEGG pathways
MAP codePathways
MAP00680Methane metabolism

Swiss-prot:Accession NumberP16099
Entry nameDHTM_METME
ActivityTrimethylamine + H(2)O + electron-transferring flavoprotein = dimethylamine + formaldehyde + reduced electron- transferring flavoprotein.
SubunitHomodimer.
Subcellular location
CofactorBinds 1 FMN covalently per subunit.,Binds 1 4Fe-4S cluster per subunit.


CofactorsSubstratesProducts
KEGG-idL00024C00061C00565C00001C04253C00543C00067C04570
Compound[4Fe-4S]FMNTrimethylamineH2OElectron-transferring flavoproteinDimethylamineFormaldehydeReduced electron-transferring flavoprotein
Typeheavy metal,sulfide groupamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ionamine groupH2Oamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,peptide/protein,phosphate group/phosphate ionamine groupcarbohydrateamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,peptide/protein,phosphate group/phosphate ion
1djnA01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
1djnB01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
1djqA01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
1djqB01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
1o94A01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
1o94B01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
1o95A01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
1o95B01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
2tmdA01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
2tmdB01Bound:SF4Bound:FMNUnbound
UnboundUnboundUnboundUnbound
1djnA02UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1djnB02UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1djqA02UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1djqB02UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1o94A02UnboundUnboundUnbound
Bound:AMP(chain C)UnboundUnboundUnbound
1o94B02UnboundUnboundUnbound
Bound:AMP(chain E)UnboundUnboundUnbound
1o95A02UnboundUnboundUnbound
Bound:AMP(chain E)UnboundUnboundUnbound
1o95B02UnboundUnboundUnbound
Bound:AMP(chain C)UnboundUnboundUnbound
2tmdA02UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
2tmdB02UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1djnA03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1djnB03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1djqA03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1djqB03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1o94A03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1o94B03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1o95A03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1o95B03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
2tmdA03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound
2tmdB03UnboundUnboundUnbound
UnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P16099 & literature [20], [31]
pdbCatalytic residuesCofactor-binding residuescomment
1djnA01TYR 60;TYR 169;HIS 172;ASP 267
CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)

1djnB01TYR 60;TYR 169;HIS 172;ASP 267
CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)

1djqA01TYR 60;TYR 169;HIS 172;ASP 267
                   ;CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
mutant C30A
1djqB01TYR 60;TYR 169;HIS 172;ASP 267
                   ;CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)
mutant C30A
1o94A01TYR 60;TYR 169;HIS 172;ASP 267
CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)

1o94B01TYR 60;TYR 169;HIS 172;ASP 267
CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)

1o95A01TYR 60;TYR 169;HIS 172;ASP 267
CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)

1o95B01TYR 60;TYR 169;HIS 172;ASP 267
CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)

2tmdA01TYR 60;TYR 169;HIS 172;ASP 267
CYS 30(FMN binding);CYS 345;CYS 348;CYS 351;CYS 364(Iron-sulfur binding)

2tmdB01TYR 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
ReferencesSectionsNo. 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]
PubMed ID6297456
JournalBiochem J
Year1982
Volume207
Pages241-52
AuthorsSteenkamp DJ, Beinert H
TitleMechanistic studies on the dehydrogenases of methylotrophic bacteria. 2. Kinetic studies on the intramolecular electron transfer in trimethylamine and dimethylamine dehydrogenase.
[2]
PubMed ID6297455
JournalBiochem J
Year1982
Volume207
Pages233-9
AuthorsSteenkamp DJ, Beinert H
TitleMechanistic 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.
[3]
PubMed ID7169636
JournalJ Mol Biol
Year1982
Volume162
Pages869-76
AuthorsLim LW, Mathews FS, Steenkamp DJ
TitleCrystallographic study of the iron-sulfur flavoprotein trimethylamine dehydrogenase from the bacterium W3A1.
[4]
PubMed ID6501301
JournalJ Biol Chem
Year1984
Volume259
Pages14458-62
AuthorsLim LW, Shamala N, Mathews FS, Steenkamp DJ
TitleMolecular structure of trimethylamine dehydrogenase from the bacterium W3A1 at 6.0-A resolution.
[5]
PubMed ID3002478
JournalBiochim Biophys Acta
Year1986
Volume869
Pages81-8
AuthorsStevenson RC, Dunham WR, Sands RH, Singer TP, Beinert H
TitleStudies on the spin-spin interaction between flavin and iron-sulfur cluster in an iron-sulfur flavoprotein.
[6]
PubMed ID3771568
JournalJ Biol Chem
Year1986
Volume261
Pages15140-6
AuthorsLim LW, Shamala N, Mathews FS, Steenkamp DJ, Hamlin R, Xuong NH
TitleThree-dimensional structure of the iron-sulfur flavoprotein trimethylamine dehydrogenase at 2.4-A resolution.
[7]
PubMed ID2545689
JournalJ Biol Chem
Year1989
Volume264
Pages11887-92
AuthorsBellamy HD, Lim LW, Mathews FS, Dunham WR
TitleStudies of crystalline trimethylamine dehydrogenase in three oxidation states and in the presence of substrate and inhibitor.
[8]
PubMed ID1917829
JournalJ Bacteriol
Year1991
Volume173
Pages5935-43
AuthorsSambasivarao D, Weiner JH
TitleDimethyl sulfoxide reductase of Escherichia coli: an investigation of function and assembly by use of in vivo complementation.
[9]
PubMed ID1651321
JournalJ Biol Chem
Year1991
Volume266
Pages15244-52
AuthorsRohlfs RJ, Hille R
TitleIntramolecular electron transfer in trimethylamine dehydrogenase from bacterium W3A1.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), AND PARTIAL SEQUENCE
Medline ID92202205
PubMed ID1551870
JournalJ Biol Chem
Year1992
Volume267
Pages6611-9
AuthorsBarber MJ, Neame PJ, Lim LW, White S, Matthews FS
TitleCorrelation of x-ray deduced and experimental amino acid sequences of trimethylamine dehydrogenase.
Related PDB2tmd
Related Swiss-protP16099
[11]
PubMed ID7983019
JournalJ Biol Chem
Year1994
Volume269
Pages30869-79
AuthorsRohlfs RJ, Hille R
TitleThe reaction of trimethylamine dehydrogenase with diethylmethylamine.
[12]
PubMed ID8188674
JournalJ Biol Chem
Year1994
Volume269
Pages13942-50
AuthorsScrutton NS, Packman LC, Mathews FS, Rohlfs RJ, Hille R
TitleAssembly 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.
[13]
PubMed ID7849604
JournalProtein Sci
Year1994
Volume3
Pages1889-92
AuthorsRaine AR, Scrutton NS, Mathews FS
TitleOn the evolution of alternate core packing in eightfold beta/alpha-barrels.
[14]
PubMed ID7673198
JournalJ Biol Chem
Year1995
Volume270
Pages22196-207
AuthorsRohlfs RJ, Huang L, Hille R
TitlePrototropic control of intramolecular electron transfer in trimethylamine dehydrogenase.
[15]
PubMed ID8810917
JournalBiochemistry
Year1996
Volume35
Pages12111-8
AuthorsFalzon L, Davidson VL
TitleIntramolecular electron transfer in trimethylamine dehydrogenase: a thermodynamic analysis.
[16]
PubMed ID8652588
JournalBiochemistry
Year1996
Volume35
Pages2445-52
AuthorsFalzon L, Davidson VL
TitleKinetic model for the regulation by substrate of intramolecular electron transfer in trimethylamine dehydrogenase.
[17]
PubMed ID8662829
JournalJ Biol Chem
Year1996
Volume271
Pages13401-6
AuthorsHuang L, Scrutton NS, Hille R
TitleReaction of the C30A mutant of trimethylamine dehydrogenase with diethylmethylamine.
[18]
PubMed ID8993316
JournalBiochemistry
Year1997
Volume36
Pages41-8
AuthorsWilson EK, Huang L, Sutcliffe MJ, Mathews FS, Hille R, Scrutton NS
TitleAn exposed tyrosine on the surface of trimethylamine dehydrogenase facilitates electron transfer to electron transferring flavoprotein: kinetics of transfer in wild-type and mutant complexes.
[19]
PubMed ID9725623
JournalProtein Eng
Year1998
Volume11
Pages447-55
AuthorsErtughrul OW, Errington N, Raza S, Sutcliffe MJ, Rowe AJ, Scrutton NS
TitleProbing the stabilizing role of C-terminal residues in trimethylamine dehydrogenase.
[20]
PubMed ID10830100
JournalBiochem Soc Trans
Year1999
Volume27
Pages767-79
AuthorsScrutton NS
TitleColworth Medal Lecture. Enzymes in the quantum world.
[21]
PubMed ID10093733
JournalBiochem Soc Trans
Year1999
Volume27
Pages196-201
AuthorsScrutton NS, Basran J, Wilson EK, Chohan KK, Jang MH, Sutcliffe MJ, Hille R
TitleElectron transfer in trimethylamine dehydrogenase and electron-transferring flavoprotein.
[22]
PubMed ID10555975
JournalBiochemistry
Year1999
Volume38
Pages14927-40
AuthorsRoberts P, Basran J, Wilson EK, Hille R, Scrutton NS
TitleRedox cycles in trimethylamine dehydrogenase and mechanism of substrate inhibition.
[23]
PubMed ID10224070
JournalJ Biol Chem
Year1999
Volume274
Pages13155-61
AuthorsBasran J, Jang MH, Sutcliffe MJ, Hille R, Scrutton NS
TitleThe role of Tyr-169 of trimethylamine dehydrogenase in substrate oxidation and magnetic interaction between FMN cofactor and the 4Fe/4S center.
[24]
PubMed ID10224069
JournalJ Biol Chem
Year1999
Volume274
Pages13147-54
AuthorsJang MH, Basran J, Scrutton NS, Hille R
TitleThe reaction of trimethylamine dehydrogenase with trimethylamine.
[25]
CommentsX-ray crystallography
PubMed ID10869173
JournalBiochemistry
Year2000
Volume39
Pages7678-88
AuthorsTrickey P, Basran J, Lian LY, Chen Z, Barton JD, Sutcliffe MJ, Scrutton NS, Mathews FS
TitleStructural and biochemical characterization of recombinant wild type and a C30A mutant of trimethylamine dehydrogenase from methylophilus methylotrophus (sp. W(3)A(1)).
Related PDB1djn,1djq
[26]
PubMed ID10859304
JournalJ Biol Chem
Year2000
Volume275
Pages30781-6
AuthorsAnderson RF, Jang MH, Hille R
TitleRadiolytic 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.
[27]
PubMed ID10777543
JournalJ Biol Chem
Year2000
Volume275
Pages12546-52
AuthorsJang MH, Scrutton NS, Hille R
TitleFormation of W(3)A(1) electron-transferring flavoprotein (ETF) hydroquinone in the trimethylamine dehydrogenase x ETF protein complex.
[28]
PubMed ID10766748
JournalJ Biol Chem
Year2000
Volume275
Pages21349-54
AuthorsJones M, Basran J, Sutcliffe MJ, Gunter Grossmann J, Scrutton NS
TitleX-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.
[29]
PubMed ID10694883
JournalTrends Biochem Sci
Year2000
Volume25
Pages126-32
AuthorsFraaije MW, Mattevi A
TitleFlavoenzymes: diverse catalysts with recurrent features.
[30]
PubMed ID11304539
JournalJ Biol Chem
Year2001
Volume276
Pages24581-7
AuthorsBasran J, Sutcliffe MJ, Scrutton NS
TitleDeuterium isotope effects during carbon-hydrogen bond cleavage by trimethylamine dehydrogenase. Implications for mechanism and vibrationally assisted hydrogen tunneling in wild-type and mutant enzymes.
[31]
PubMed ID11553643
JournalJ Biol Chem
Year2001
Volume276
Pages42887-92
AuthorsBasran J, Sutcliffe MJ, Scrutton NS
TitleOptimizing the Michaelis complex of trimethylamine dehydrogenase: identification of interactions that perturb the ionization of substrate and facilitate catalysis with trimethylamine base.
[32]
PubMed ID11429403
JournalJ Biol Chem
Year2001
Volume276
Pages34142-7
AuthorsChohan KK, Jones M, Grossmann JG, Frerman FE, Scrutton NS, Sutcliffe MJ
TitleProtein dynamics enhance electronic coupling in electron transfer complexes.
[33]
PubMed ID11336819
JournalTrends Microbiol
Year2001
Volume9
Pages196-8
AuthorsSargent F
TitleA marriage of bacteriology with cell biology results in twin arginines.
[34]
PubMed ID12084049
JournalEur J Biochem
Year2002
Volume269
Pages3096-102
AuthorsSutcliffe MJ, Scrutton NS
TitleA new conceptual framework for enzyme catalysis. Hydrogen tunnelling coupled to enzyme dynamics in flavoprotein and quinoprotein enzymes.
[35]
PubMed ID11756429
JournalJ Biol Chem
Year2002
Volume277
Pages8457-65
AuthorsJones M, Talfournier F, Bobrov A, Grossmann JG, Vekshin N, Sutcliffe MJ, Scrutton NS
TitleElectron transfer and conformational change in complexes of trimethylamine dehydrogenase and electron transferring flavoprotein.
[36]
CommentsX-ray crystallography
PubMed ID12567183
JournalNat Struct Biol
Year2003
Volume10
Pages219-25
AuthorsLeys D, Basran J, Talfournier F, Sutcliffe MJ, Scrutton NS
TitleExtensive conformational sampling in a ternary electron transfer complex.
Related PDB1o94,1o95

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).

createdupdated
2004-12-162009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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