Information on EC 1.14.13.148 - trimethylamine monooxygenase

New: Word Map on EC 1.14.13.148
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
1.14.13.148
-
RECOMMENDED NAME
GeneOntology No.
trimethylamine monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
N,N,N-trimethylamine + NADPH + H+ + O2 = N,N,N-trimethylamine N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Methane metabolism
-
-
trimethylamine degradation
-
-
SYSTEMATIC NAME
IUBMB Comments
N,N,N-trimethylamine,NADPH:oxygen oxidoreductase (N-oxide-forming)
A flavoprotein. The bacterial enzyme enables bacteria to use trimethylamine as the sole source of carbon and energy [1,4]. The mammalian enzyme is involved in detoxification of trimethylamine. Mutations in the human enzyme cause the inheritable disease known as trimethylaminuria (fish odor syndrome) [2,3].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
beagle
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
no activity in Dinoroseobacter shibae
-
-
-
Manually annotated by BRENDA team
no activity in Oceanicola batsensis
-
-
-
Manually annotated by BRENDA team
no activity in Roseobacter sp.
-
-
-
Manually annotated by BRENDA team
no activity in Roseobacter sp. SK209-2-6
-
-
-
Manually annotated by BRENDA team
no activity in Sagittula stellata
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
-
isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
10-[(N,N-dimethylaminopentyl)]-2-(trifluoromethylphenothiazine) + NADPH + H+ + O2
?
show the reaction diagram
-
functional substrate
-
-
?
3-dimethylaminopropan-1-ol + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
3-dimethylaminopropan-2-ol + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
5-{[3-(dimethylamino)propyl]amino}-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one + NADPH + H+ + O2
5-{[3-(dimethylnitroryl)propyl]amino}-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one + NADP+ + H2O
show the reaction diagram
5-{[3-(dimethylamino)propyl]amino}-8-methoxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one + NADPH + H+ + O2
5-{[3-(dimethylnitroryl)propyl]amino}-8-methoxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one + NADP+ + H2O
show the reaction diagram
benzydamine + NADPH + H+ + O2
benzydamine N-oxide + NADP+ + H2O
show the reaction diagram
benzydamine + NADPH + H+ + O2
benzylamine N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
cysteamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
danusertib + NADPH + H+ + O2
danusertib N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
diethylmethylamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
dimethylaniline + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
dimethylsulfide + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
DMSO + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
ethionamide + NADPH + H+ + O2
ethionamide S-oxide + NADP+ + H2O
show the reaction diagram
ethyldimethylamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
methimazole + NADPH + H+ + O2
?
show the reaction diagram
methimazole + NADPH + H+ + O2
methimazole N-oxide + NADP+ + H2O
show the reaction diagram
methyl 4-tolyl sulfide + NADPH + H+ + O2
methyl 4-tolyl sulfoxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
N,N,N-trimethylamine + NADH + H+ + O2
N,N,N-trimethylamine N-oxide + NAD+ + H2O
show the reaction diagram
-
-
-
-
?
N,N,N-trimethylamine + NADPH + H+ + O2
N,N,N-trimethylamine N-oxide + NADP+ + H2O
show the reaction diagram
N,N-dimethyl-2-chloroethylamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
N,N-dimethylamine + NADPH + H+ + O2
N,N-dimethylamine N-oxide + NADP+ + H2O
show the reaction diagram
N,N-dimethylaniline + NADPH + H+ + O2
N,N-dimethylaniline N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
N,N-dimethylbutylamine + NADPH + H+ + O2
N,N-dimethylbutylamine N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
N,N-dimethylethanolamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
N,N-dimethylethylenediamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
N,N-dimethylpropylenediamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
sulindac sulfide + NADPH + H+ + O2
sulindac + NADP+ + H2O
show the reaction diagram
tozasertib + NADPH + H+ + O2
tozasertib N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
triethylamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
tyramine + NADPH + H+ + O2
-
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
no activity with N-monomethylamine, glutathione, and cysteine
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
N,N,N-trimethylamine + NADPH + H+ + O2
N,N,N-trimethylamine N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-dimethylaminopropan-1-ol
-
inhibitory at concentrations above about 1 mM
3-dimethylaminopropan-2-ol
-
inhibitory at concentrations above about 1 mM
Cu2+
-
0.2 mM Cu2+ inhibits the enzyme strongly without any preincubation
diethylmethylamine
-
inhibitory at concentrations above about 1 mM
ethyldimethylamine
-
inhibitory at concentrations above about 1 mM
N,N-dimethyl-2-chloroethylamine
-
inhibitory at concentrations above about 1 mM
N,N-dimethylethanolamine
-
inhibitory at concentrations above about 1 mM
N,N-dimethylethylenediamine
-
inhibitory at concentrations above about 1 mM
N,N-dimethylpropylenediamine
-
inhibitory at concentrations above about 1 mM
N-ethylmaleimide
-
preincubation of the enzyme for 15 min at 14C, pH 7.7, in the presence of 1.0 mM N-ethylmaleimide inhibits the enzymatic activity approximately by 25%
p-chloromercuribenzoate
-
preincubation of the enzyme for 15 min at 14C, pH 7.7, in the presence of 0.2 mM p-chloromercuribenzoate inhibits the enzymic activity approximately by 90%
Thiourea
triethylamine
-
inhibitory at concentrations above about 1 mM
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
chlorpromazine
-
the activity of the native enzyme is increased at 0.001-0.2 mM of chlorpromazine. Greatest activation is 85% when methimazole and chlorpromazine concentrations are 2 mM and 0.1 mM, respectively
imipramine
-
the activity of the native enzyme is increased at 0.05-0.75 mM of imipramine
O2
-
when the oxygen in the enzyme assay mixture is replaced with 100% nitrogen, there is no formation of N,N,N-trimethylamine N-oxide, showing that the enzyme is oxygen-dependent
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1116
5-{[3-(dimethylamino)propyl]amino}-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one
isozyme FMO3, in 0.1 M potassium phosphate buffer (pH 8.4) at 37C
0.1624
5-{[3-(dimethylamino)propyl]amino}-8-methoxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one
isozyme FMO3, in 0.1 M potassium phosphate buffer (pH 8.4) at 37C
0.0186 - 0.056
Benzydamine
3.139
cysteamine
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
0.0357
dimethylaniline
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
0.0103
Dimethylsulfide
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
3.575
DMSO
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
0.114 - 0.336
Ethionamide
0.0282 - 0.035
Methimazole
0.0003 - 0.0548
N,N,N-trimethylamine
0.0897
N,N-dimethylamine
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
2
NADH
-
pH and temperature not specified in the publication
0.0008 - 0.016
NADPH
0.022 - 0.0693
sulindac sulfide
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.973 - 1.01
Ethionamide
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00047
-
supernatant of homogenate, in potassium diphosphate buffer (pH 7.7), at 14C
0.025
isoform FMO3, using 1 mM methimazole as substrate, at pH 8.4, temperature not specified in the publication
0.049
-
crude enzyme from membranes, using methyl 4-tolyl sulfide as substrate, in 25 mM potassium diphosphate (pH 8.5), at 37C
0.085
-
after 180fold purification, in potassium diphosphate buffer (pH 7.7), at 14C
0.201
-
after purification, using methyl 4-tolyl sulfide as substrate, in 25 mM potassium diphosphate (pH 8.5), at 37C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4 - 8.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
isoform FMO4 is most prominent in the kidney
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
130000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
N-linked glycosylation at Asn61 and O-linked glycosylation at Thr29, Thr249, and Thr381. Posttranslational modification of human FMO3 by insect cells is limited to cleavage at the N-terminal methionine
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 9
-
the enzyme is stable at 0C for 30min at any pH value in the range 4.0-9.0
717207
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0 - 20
-
the enzyme is stable for 30 min at temperatures between 0 and 20C, when the enzyme is preincubated for 30 min at temperatures above 20C, a decrease in enzymic activity ensues
35
-
the enzyme has a half-life in the crude extract of 20 min at 35C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
addition of FAD and dithiothreitol together with NADPH improves the stability of the enzyme
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, Sephadex G-200 gel filtration, DEAE-cellulose column chromatography, and calcium phosphate chromatography
-
cholate solubilization and sequential column chromatography on octyl-Sepharose, DEAE-Sepharose, and hydroxyapatite
-
DEAE ion exchange column chromatography and Ni affinity column chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli BLR(DE3) pLysS cells
expressed in Saccharomyces cerevisiae strain 334 and in Escherichia coli JM109 cells; expressed in Saccharomyces cerevisiae strain 334 and in Escherichia coli JM109 cells
expressed in Sf9 insect cells
expressed in Spodoptera frugiperda insect cells using a baculovirus expression system
-
expressed in Trichoplusia ni cells and in Escherichia coli strain XL-1 Blue
-
expressed in Trichoplusia ni cells using a baculovirus expression vector system
-
wild type and truncated enzymes are expressed in Escherichia coli JM109 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
5-aza-2'-deoxycytidine at 0.001 mM and 0.0025 mM results in 6.6fold and 9.2fold increases in FMO3 mRNA levels, respectively. HNF4alpha transient expression results in a 3.1fold increase in FMO3 mRNA levels. Co-transfection of HepG2 cells with the CCAAT/enhancer-binding protein beta expression vector and the pRNH694 reporter construct results in a dose-dependent increase in FMO3 promoter activity with a maximal 2fold increase using 0.001 mg of expression
-
no changes in relative FMO3 mRNA levels are observed with 50 nM trichostatin A
-
the enzyme is absent during growth on methanol
-
the enzyme is highly expressed in N,N,N-trimethylamine-grown Methylocella silvestris
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E24D
-
the mutation impacts the structure of the Rossmann fold involved in FAD binding and does not alter FMO3 catalytic activity
E305X
-
the mutation is associated with trimethylaminuria
K416N
-
the mutation has minimal impact on either hydrophilicity or protein structure
M66I
-
the mutation is associated with trimethylaminuria
N245N
-
the mutation is associated with trimethylaminuria
N61K
-
the mutation disrupts the secondary structure of a conserved membrane interaction domain and does not alter FMO3 catalytic activity
P153L
-
the mutation is associated with trimethylaminuria
P153L/E305X
-
the mutation is associated with trimethylaminuria
S310S
-
the mutation is associated with trimethylaminuria
T428R
-
methimazole activity of the mutant enzyme is stimulated (maximally 25% when the methimazole concentration is 2 mM) to the same extend of native enzyme up to an imipramine concentration of 3 mM. The activity of the mutant is inhibited at concentrations above 0.3 mM imipramine, 0.75 mM imipramine causes 93% inhibition of methimazole activity of the mutant enzyme. Chlorpromazine activates the mutant enzyme only at high substrate concentrations (0.1-2 mM)