Information on EC 1.14.13.148 - trimethylamine monooxygenase

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

EC NUMBER
COMMENTARY
1.14.13.148
-
RECOMMENDED NAME
GeneOntology No.
trimethylamine monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
N,N,N-trimethylamine + NADPH + H+ + O2 = N,N,N-trimethylamine N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
PATHWAY
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].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
EC 1.14.13.8
-
assigned to
EC 1.14.13.8
P31513
assigned to
EC 1.14.13.8
P32417, P36367
assigned to
FAD-containing monooxygenase
-
-
flavin containing monooxygenase 3
-
-
flavin monooxygenase 3
-
-
flavin-containing monooxygenase
-
-
flavin-containing monooxygenase
Candidatus Pelagibacter ubique HTCC1002, Candidatus Pelagibacter ubique HTCC7211
-
-
-
flavin-containing monooxygenase
-
-
flavin-containing monooxygenase
P31513
-
flavin-containing monooxygenase
-
-
flavin-containing monooxygenase
P97501
-
flavin-containing monooxygenase
P32417, P36367
-
flavin-containing monooxygenase
-
-
flavin-containing monooxygenase
Roseovarius sp.
-
-
flavin-containing monooxygenase
-
-
-
flavin-containing monooxygenase
-
-
flavin-containing monooxygenase 3
-
-
flavin-containing monooxygenase 3
-
-
flavin-containing monooxygenase 3
P31513
-
FMO
Candidatus Pelagibacter ubique HTCC1002, Candidatus Pelagibacter ubique HTCC7211
-
-
-
FMO
Roseovarius sp.
-
-
FMO3
-
isoform
FMO3
-
most active isoform
FMO3
P31513
-
FMO3
P31513
isozyme
FMO3
P97501
isozyme
FMO3
P32417
isoform
FMO3
-
isozyme
FMO4
P36367
isoform
TMA monooxygenase
-
-
TMA monooxygenase
-
-
TMA monooxygenase
Candidatus Pelagibacter ubique HTCC1002, Candidatus Pelagibacter ubique HTCC7211
-
-
-
TMA monooxygenase
Methylocella silvestris, Roseovarius sp.
-
-
TMA monooxygenase
-
-
-
TMA monooxygenase
-
-
TMA N-oxygenase
-
-
TMM
Candidatus Pelagibacter ubique HTCC1002, Candidatus Pelagibacter ubique HTCC7211
-
-
-
TMM
Methylocella silvestris, Roseovarius sp.
-
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Candidatus Pelagibacter ubique HTCC7211
-
-
-
Manually annotated by BRENDA team
isozyme FMO3
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
isoform FMO3
UniProt
Manually annotated by BRENDA team
isoform FMO4
UniProt
Manually annotated by BRENDA team
Roseovarius sp.
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase
malfunction
-
mutations of the flavin-containing monooxygenase gene FMO3 cause trimethylaminuria
malfunction
-
FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome
metabolism
-
isoform FMO3 in human liver may contribute to the toxicity and/or affect efficacy of ethionamide administration
metabolism
P31513
the flavin monooxygenase FMO3 contributes to metabolism of anti-tumour triazoloacridinone, C-1305 (5-dimethylaminopropylamino-8-hydroxytriazoloacridinone), in liver microsomes and Hep-G2 cells
metabolism
-
the flavin monooxygenase FMO3 contributes to metabolism of anti-tumour triazoloacridinone, C-1305 (5-dimethylaminopropylamino-8-hydroxytriazoloacridinone), in liver microsomes
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 ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
-
-
-
?
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
-
-
-
-
?
C-1299 + NADPH + H+ + O2
C-1299 N-oxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
C-1299 + NADPH + H+ + O2
C-1299 N-oxide + NADP+ + H2O
show the reaction diagram
P31513
-
-
-
?
C-1305 + NADPH + H+ + O2
C-1305 N-oxide + NADP+ + H2O
show the reaction diagram
-
i.e. 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone
-
-
?
C-1305 + NADPH + H+ + O2
C-1305 N-oxide + NADP+ + H2O
show the reaction diagram
P31513
i.e. 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone
-
-
?
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
P31513
-
-
-
?
ethionamide + NADPH + H+ + O2
ethionamide S-oxide + NADP+ + H2O
show the reaction diagram
P97501
-
-
-
?
ethyldimethylamine + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
methimazole + 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
-
-
-
-
?
methimazole + NADPH + H+ + O2
methimazole N-oxide + NADP+ + H2O
show the reaction diagram
P32417, P36367
-
-
-
?
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,N-trimethylamine + NADPH + H+ + O2
N,N,N-trimethylamine N-oxide + NADP+ + 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,N-trimethylamine + NADPH + H+ + O2
N,N,N-trimethylamine N-oxide + NADP+ + H2O
show the reaction diagram
Ruegeria pomeroyi, Roseovarius sp.
-
-
-
-
?
N,N,N-trimethylamine + NADPH + H+ + O2
N,N,N-trimethylamine N-oxide + NADP+ + 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,N-trimethylamine + NADPH + H+ + O2
N,N,N-trimethylamine N-oxide + NADP+ + H2O
show the reaction diagram
-
highest affinity substrate
-
-
?
N,N,N-trimethylamine + NADPH + H+ + O2
N,N,N-trimethylamine N-oxide + NADP+ + H2O
show the reaction diagram
Candidatus Pelagibacter ubique HTCC7211, Candidatus Pelagibacter ubique HTCC1002, Roseovarius sp. 217
-
-
-
-
?
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-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
-
-
-
-
?
sulindac sulfide + NADPH + H+ + O2
sulindac + NADP+ + H2O
show the reaction diagram
-
the enzyme does not display saturability at concentrations through 1 mM of sulindac sulfide
-
-
?
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
-
-
-
-
?
methyl 4-tolyl sulfide + NADPH + H+ + O2
methyl 4-tolyl sulfoxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
no activity with N-monomethylamine, glutathione, and cysteine
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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 ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
FAD
P32417, P36367
;
NADPH
-
dependent on
NADPH
P97501
required for activity
NADPH
-
dependent on, preferred electron donor over NADH
NADPH
-
dependent on, in the absence of NADPH the enzyme is rapidly and irreversibly inactivated at 0-5C. NADP+ also stabilizes the enzyme, but to a lesser extent than NADPH. No oxidation of N,N,N-trimethylamine is observed when NADH is used in the enzyme assay instead of NADPH
NADPH
-
required for activity, in the absence of NADP or NADPH, the FAD-containing monooxygenase is irreversibly inactivated at 37C during 30 min
NADPH
-
dependent on
NADPH
-
required
NADPH
P32417, P36367
required for activity; required for activity
NADPH
-
required for activity
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
the enzyme shows no metal ion requirement
additional information
-
no metal ion activators are found
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3-dimethylaminopropan-1-ol
-
inhibitory at concentrations above about 1 mM
-
3-dimethylaminopropan-2-ol
-
inhibitory at concentrations above about 1 mM
-
Chlorpromazine
P32417, P36367
;
Cu2+
-
0.2 mM Cu2+ inhibits the enzyme strongly without any preincubation
diethylmethylamine
-
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%
prochlorperazine
P32417, P36367
;
Thiourea
P97501
thiourea reduces ethionamide oxygenation to ethionamide S-oxide by an average of 73.5% in liver and 76.9% in lung
triethylamine
-
inhibitory at concentrations above about 1 mM
ethyldimethylamine
-
inhibitory at concentrations above about 1 mM
additional information
-
the enzyme is not inhibited by CO, cyanide or SKF 525-A (2-diethylaminoethyl 2,2-diphenylvalerate hydrochloride), nor by chelating agents
-
additional information
-
10 mM EDTA, 1 mM potassium cyanide and 1 mM sodium azide do not inhibit the enzyme. Bubbling the enzyme solution with CO for 2 min at 0C or including CO (CO:O2 ratio 1:1) during the tests has no effect on enzyme activity
-
additional information
-
enzyme reactions are not inhibited by gas phase containing up to 80% carbon monoxide/20% oxygen mixture
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
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
imipramine
-
the activity of the native enzyme is increased at 0.05-0.75 mM of imipramine
additional information
P32417, P36367
n-octylamine has no effect on isoform FMO3
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0186
-
Benzydamine
-
in in 0.1 M tricine buffer, pH 7.4, at 37C
0.0426
-
Benzydamine
-
in in 0.1 M tricine buffer, pH 7.4, at 37C
0.045
-
Benzydamine
-
truncated recombinant enzyme, in 50 mM potassium phosphate buffer (pH 7.4), at 37C
0.056
-
Benzydamine
-
wild type enzyme, in 50 mM potassium phosphate buffer (pH 7.4), at 37C
0.1624
-
C-1299
P31513
isozyme FMO3, in 0.1 M potassium phosphate buffer (pH 8.4) at 37C
-
0.1116
-
C-1305
P31513
isozyme FMO3, in 0.1 M potassium phosphate buffer (pH 8.4) at 37C
-
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
-
Ethionamide
P97501
isozyme FMO3, at pH 9.5 and 37C
0.336
-
Ethionamide
-
isozyme FMO3, at pH 9.5 and 37C
0.0282
-
Methimazole
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
0.0285
-
Methimazole
-
mutant enzyme, at pH and 37C
0.03
-
Methimazole
-
native enzyme, at pH and 37C
0.03
-
Methimazole
P32417, P36367
isoform FMO3, at pH 8.4, temperature not specified in the publication
0.033
-
Methimazole
-
wild type enzyme, in 50 mM potassium phosphate buffer (pH 7.4), at 37C
0.035
-
Methimazole
-
truncated recombinant enzyme, in 50 mM potassium phosphate buffer (pH 7.4), at 37C
0.0003
-
N,N,N-trimethylamine
-
in potassium diphosphate buffer (pH 7.7), at 14C
0.0094
-
N,N,N-trimethylamine
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
0.013
0.0548
N,N,N-trimethylamine
-
the Km for isoform FMO3 determined in human liver microsomes ranges from 0.013.to 0.0548 mM, at pH 7.4 and 22C
0.0208
-
N,N,N-trimethylamine
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
0.0216
-
N,N,N-trimethylamine
Roseovarius sp.
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
0.0275
-
N,N,N-trimethylamine
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
0.028
-
N,N,N-trimethylamine
-
recombinant isoform FMO3, at pH 7.4 and 22C
0.0285
-
N,N,N-trimethylamine
-
recombinant enzyme, in 80 mM PIPES buffer (pH 7.6), at 22C
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
-
NADPH
-
in potassium diphosphate buffer (pH 7.7), at 14C
0.016
-
NADPH
-
pH and temperature not specified in the publication
0.022
-
sulindac sulfide
-
truncated recombinant enzyme, in 50 mM potassium phosphate buffer (pH 7.4), at 37C
0.025
-
sulindac sulfide
-
wild type enzyme, in 50 mM potassium phosphate buffer (pH 7.4), at 37C
0.0693
-
sulindac sulfide
-
in in 0.1 M tricine buffer, pH 9.0, at 37C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.973
-
Ethionamide
-
isozyme FMO3, at pH 9.5 and 37C
1.01
-
Ethionamide
P97501
isozyme FMO3, at pH 9.5 and 37C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00047
-
-
supernatant of homogenate, in potassium diphosphate buffer (pH 7.7), at 14C
0.025
-
P32417, P36367
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
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
8.4
P31513
the activity is approximately twice as high at pH 8.4 as at pH 7.4
7.4
8.4
-
the activity is approximately twice as high at pH 8.4 as at pH 7.4
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
P32417, P36367
isoform FMO4 is most prominent in the kidney
Manually annotated by BRENDA team
-
FMO3 is the major hepatic isozyme in adults
Manually annotated by BRENDA team
-
adult liver
Manually annotated by BRENDA team
-
FMO3 is quantitatively a major human liver monooxygenase
Manually annotated by BRENDA team
-
FMO3 is the major form of flavin-containing monooxygenase expressed in adult human liver
Manually annotated by BRENDA team
P32417, P36367
isoform FMO3 is most prominent in the liver
Manually annotated by BRENDA team
additional information
-
FMO3 is not expressed in HepG2 cells
Manually annotated by BRENDA team
additional information
-
no activity in fetal human liver, intestine, and kidney
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
130000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 56000, SDS-PAGE
?
-
x * 60000, SDS-PAGE
?
P32417, P36367
59815, isofom FMO3, calculated from amino acid sequence; x * 62992, isoform FMO4, calculated from amino acid sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
9
-
the enzyme is stable at 0C for 30min at any pH value in the range 4.0-9.0
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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 ACCESSION NO.
LITERATURE
addition of FAD and dithiothreitol together with NADPH improves the stability of the enzyme
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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 ACCESSION NO.
LITERATURE
expressed in Escherichia coli BLR(DE3) pLysS cells
-
expressed in Spodoptera frugiperda insect cells using a baculovirus expression system
-
expressed in Escherichia coli
-
expressed in Sf9 insect cells
-
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
-
expressed in Escherichia coli BLR(DE3) pLysS cells
-
expressed in Sf9 insect cells
P97501
expressed in Saccharomyces cerevisiae strain 334 and in Escherichia coli JM109 cells; expressed in Saccharomyces cerevisiae strain 334 and in Escherichia coli JM109 cells
P32417, P36367
expressed in Escherichia coli BLR(DE3) pLysS cells
Roseovarius sp., Ruegeria pomeroyi
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
no changes in relative FMO3 mRNA levels are observed with 50 nM trichostatin A
-
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
-
the enzyme is absent during growth on methanol
-
the enzyme is highly expressed in N,N,N-trimethylamine-grown Methylocella silvestris
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E158K
-
the mutation is associated with trimethylaminuria
E158K
-
the mutant shows reduced FMO3 activity
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
E308G
-
the mutation is associated with trimethylaminuria
E308G
-
the mutant shows reduced FMO3 activity
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)
V257M
-
the mutation is associated with trimethylaminuria
V257M
-
the mutant shows reduced FMO3 activity