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Information on EC 1.14.13.8 - flavin-containing monooxygenase and Organism(s) Oryctolagus cuniculus and UniProt Accession P17635
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1.14.13.8 flavin-containing monooxygenaseIUBMB Comments
A flavoprotein. A broad spectrum monooxygenase that accepts substrates as diverse as hydrazines, phosphines, boron-containing compounds, sulfides, selenides, iodide, as well as primary, secondary and tertiary amines [3,4]. This enzyme is distinct from other monooxygenases in that the enzyme forms a relatively stable hydroperoxy flavin intermediate [4,5]. This microsomal enzyme generally converts nucleophilic heteroatom-containing chemicals and drugs into harmless, readily excreted metabolites. For example, N-oxygenation is largely responsible for the detoxification of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [2,6]
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Word Map
- 1.14.13.8
-
orbit
- methimazole
- trimethylamine
- xenobiotics
-
fenna-matthews-olson
- sulfoxide
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n-oxygenation
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excitonic
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s-oxidation
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initio
- bacteriochlorophyll
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frontier
-
n-demethylation
- antenna
- tepidum
-
drug-metabolizing
- thioureas
- n-octylamine
- phenobarbital
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cdna-expressed
-
light-harvesting
-
pigment-protein
- imipramine
- metyrapone
-
yucca
- chlorobium
-
baeyer-villiger
- cyp2c19
-
n-hydroxylation
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diels-alder
-
hamiltonians
-
monooxygenation
-
sulfenic
-
p-450-dependent
- trimethylamine-n-oxide
- aestuarii
- cyp2a6
- nitrone
-
malodor
-
hartree-fock
- 1-aminobenzotriazole
-
ifies
-
piperonyl
- drug development
The taxonomic range for the selected organisms is: Oryctolagus cuniculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
fmo, flavin-containing monooxygenase, flavin monooxygenase, flavin-dependent monooxygenase, flavin-containing monooxygenase 3, fad-containing monooxygenase, flavoprotein monooxygenase, hfmo3, flavin-containing mono-oxygenase, flavin-containing monooxygenase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dimethylaniline monooxygenase (N-oxide-forming)
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-
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dimethylaniline N-oxidase
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-
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dimethylaniline oxidase
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-
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DMA oxidase
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-
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FAD-containing monooxygenase
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flavin monooxygenase
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flavin-containing monooxygenase
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FMO
FMO 1A1
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-
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FMO 1B1
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-
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FMO 1C1
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-
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FMO 1D1
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-
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FMO 1E1
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-
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FMO-I
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-
-
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FMO-II
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-
-
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FMO1
FMO2
FMO3
FMO5
mixed-function amine oxidase
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-
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N,N-dimethylaniline monooxygenase
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oxygenase, dimethylaniline mono- (N-oxide-forming)
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oxygenase, methylphenyltetrahydropyridine N-mono-
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FMO
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FMO1
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FMO2
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-
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FMO3
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FMO5
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O
catalytic cycle and catalytic reaction mechanism, structure-function relationship, FMO oxygenates drugs and xenobiotics containing a soft nucleophile, usually nitrogen or sulfur, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate, FMO does not require a reductase to transfer electrons from NADPH, substrate binding has no effect on velocity, formation of a peroxyflavin intermediate
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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-
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oxidation
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reduction
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SYSTEMATIC NAME
IUBMB Comments
N,N-dimethylaniline,NADPH:oxygen oxidoreductase (N-oxide-forming)
A flavoprotein. A broad spectrum monooxygenase that accepts substrates as diverse as hydrazines, phosphines, boron-containing compounds, sulfides, selenides, iodide, as well as primary, secondary and tertiary amines [3,4]. This enzyme is distinct from other monooxygenases in that the enzyme forms a relatively stable hydroperoxy flavin intermediate [4,5]. This microsomal enzyme generally converts nucleophilic heteroatom-containing chemicals and drugs into harmless, readily excreted metabolites. For example, N-oxygenation is largely responsible for the detoxification of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [2,6]
CAS REGISTRY NUMBER
COMMENTARY
117910-56-2
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148848-55-9
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37256-46-5
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37256-73-8
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
10-(N,N-dimethylaminoalkyl)-2-(trifluoromethyl) phenothiazines + NADPH + O2
?
-
with the alkyl side chain varying in length from 5 to 7 carbons, no activity with shorter side chains by isozyme FMO2
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-
?
benzydamine + NADPH + H+ + O2
benzydamine N-oxide + NADP+ + H2O
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-
-
-
?
L-Met-Phe + NADPH + O2
(L-Met-S-oxide)-Phe + NADP+ + H2O
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liver microsomes
-
-
?
L-Met-Val + NADPH + O2
(L-Met-S-oxide)-Val + NADP+ + H2O
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liver microsomes
-
-
?
L-Phe-Met + NADPH + O2
(L-Met-S-oxide)-Phe + NADP+ + H2O
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liver microsomes
-
-
?
L-seleno-methionine + NADPH + O2
L-methionine seleno-oxide + NADP+ + H2O
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liver microsomes
-
-
?
methimazole + NADPH + O2
N-methylmethimidazole-2-sulfinic acid + NADP+ + H2O
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-
-
-
?
N,N-dimethylaniline + NADPH + O2
N,N-dimethylaniline N-oxide + NADP+ + H2O
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-
-
-
?
n-decylamine + NADPH + O2
1-nitrosodecane + NADP+ + H2O
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lung enzyme active, liver enzyme not
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-
?
n-octylamine + NADPH + O2
1-nitrosooctane + NADP+ + H2O
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lung enzyme active, liver enzyme not
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-
?
naphthylthiourea + NADPH + O2
naphthylthiourea S-oxide + NADP+ + H2O
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isozyme FMO2
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-
?
phenylthiourea + NADPH + O2
phenylthiourea S-oxide + NADP+ + H2O
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isozyme FMO2
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-
?
L-methionine + NADPH + O2
L-methionine S-oxide + NADP+ + H2O
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-
-
-
?
L-methionine + NADPH + O2
L-methionine S-oxide + NADP+ + H2O
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free and N-terminally peptide-bound L-methionine, no activity with modified peptide-bound methionine and with N-acetyl-L-methionine, isozymes FMO1-FMO4
stereospecificity for formation of the D-isomer, especially by isozyme FMO3
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?
additional information
?
-
the enzyme is involved in oxidative metabolism of drugs and other chemicals
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-
?
additional information
?
-
-
the enzyme is involved in oxidative metabolism of drugs and other chemicals
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-
?
additional information
?
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-
nitrogen- and sulfur-containing endogenous substrates and physiologic functions, the enzyme is involved in detoxification and drug metabolism, overview
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-
?
additional information
?
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stereoselectivity of recombinant isozymes FMO1, FMO2, and FMO3
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-
?
additional information
?
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the lung isozyme is distinct from the liver isozyme in having high activity toward primary alkyl amines, restricted substrate specificity related to steric properties, resistance to detergent inhibition and enhanced thermal stability, and restricted substrate access, no activity of the lung isozyme with 1,3-diphenylthiourea, chlorpromazine and imipramine by isozyme FMO2, isozyme substrate specificity, detailed overview
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-
?
additional information
?
-
-
benzydamine is a weak base and an indazole derivative with analgesic and antipyretic properties used in human and veterinary medicine, it is metabolized to a wide range of metabolites. One of the main metabolites, benzydamine N-oxide is produced in the liver and brain by flavin-containing monooxygenases
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
benzydamine + NADPH + H+ + O2
benzydamine N-oxide + NADP+ + H2O
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-
-
-
?
L-methionine + NADPH + O2
L-methionine S-oxide + NADP+ + H2O
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-
-
-
?
N,N-dimethylaniline + NADPH + O2
N,N-dimethylaniline N-oxide + NADP+ + H2O
-
-
-
-
?
additional information
?
-
the enzyme is involved in oxidative metabolism of drugs and other chemicals
-
-
?
additional information
?
-
-
the enzyme is involved in oxidative metabolism of drugs and other chemicals
-
-
?
additional information
?
-
-
nitrogen- and sulfur-containing endogenous substrates and physiologic functions, the enzyme is involved in detoxification and drug metabolism, overview
-
-
?
additional information
?
-
-
benzydamine is a weak base and an indazole derivative with analgesic and antipyretic properties used in human and veterinary medicine, it is metabolized to a wide range of metabolites. One of the main metabolites, benzydamine N-oxide is produced in the liver and brain by flavin-containing monooxygenases
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
n-decyl-beta-D-maltoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-dodecyl-beta-D-maltoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-dodecyl-N,N-dimethylamine-n-oxide
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-nonyl-beta-D-glucoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-octyl-beta-D-glucoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-octyl-beta-D-thioglucoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
additional information
-
the lung isozyme is resistant to detergent inhibition
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
n-decyl-beta-D-maltoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-dodecyl-beta-D-maltoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-dodecyl-N,N-dimethylamine-n-oxide
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-nonyl-beta-D-glucoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-octyl-beta-D-glucoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-octyl-beta-D-thioglucoside
1%, activates at pH 7.5-8.5, inhibits at pH 9.5, mutant and wild-type enzymes
n-octylamine
-
allosteric activation of pig liver and mouse lung enzymes, not mouse, rabbit or rat liver enzymes
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
Michaelis-Menten kinetics, overview
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
inhibition kinetics, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
9.8
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.6 - 9.6
-
about 50% of activity maximum at pH 7.6 and 9.6, liver, thiobenzamide S-oxidation
8.4 - 10.4
-
about 50% of activity maximum at pH 8.4 and 10.4, lung, thiobenzamide S-oxidation
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
-
differential expression of isozymes in tissues
additional information
-
the lung isozyme FMO2 is distinct from the liver isozyme in having high activity toward primary alkyl amines, restricted substrate specificity related to steric properties, resistance to detergent inhibition and enhanced thermal stability
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). FMO2_RABIT
535
1
61144
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
structure motifs, overview, structural modeling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
C-terminal truncation of 26 amino acids and and a double Ser substitutio of isozyme FMO2 enhances the enzyme solubility and reduce hydrophobicity required for efficient enzyme crystallization, overview
additional information
-
C-terminal truncation of 26 amino acids and and a double Ser substitutio of isozyme FMO2 enhances the enzyme solubility and reduce hydrophobicity required for efficient enzyme crystallization, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the lung isozyme shows high thermal stability as the liver isozyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of N-terminally His6-tagged truncation mutant in Escherichia coli as soluble enzyme, and expression of the mutant in Spodoptera frugiperda Sf9 insect cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tynes, R.E.; Sabourin, P.J.; Hodgson, E.
Identification of distinct hepatic and pulmonary forms of microsomal flavin-containing monooxygenase in the mouse and rabbit
Biochem. Biophys. Res. Commun.
126
1069-1075
1985
Oryctolagus cuniculus, Mus musculus
Guan, S.; Falick, A.M.; Williams, D.E.; Cashman, J.R.
Evidence for complex formation between rabbit lung flavin-containing monooxygenase and calreticulin
Biochemistry
30
9892-9900
1991
Oryctolagus cuniculus
Lawton, M.P.; Gasser, R.; Tynes, R.E.; Hodgson, E.; Philpot, R.M.
The flavin-containing monooxygenase enzymes expressed in rabbit liver and lung are products of related but distinctly different genes
J. Biol. Chem.
265
5855-5861
1990
Oryctolagus cuniculus
Tynes, R.E.; Hodgson, E.
Catalytic activity and substrate specificity of the flavin-containing monooxygenase in microsomal systems: characterization of the hepatic, pulmonary and renal enzymes of the mouse, rabbit, and rat
Arch. Biochem. Biophys.
240
77-93
1985
Oryctolagus cuniculus, Mus musculus, Rattus norvegicus, Sus scrofa
Krueger, S.K.; Siddens, L.K.; Henderson, M.C.; VanDyke, J.E.; Karplus, P.A.; Pereira, C.B.; Williams, D.E.
C-terminal truncation of rabbit flavin-containing monooxygenase isoform 2 enhances solubility
Arch. Biochem. Biophys.
450
149-156
2006
Oryctolagus cuniculus (P17635), Oryctolagus cuniculus
Elfarra, A.A.; Krause, R.J.
Potential roles of flavin-containing monooxygenases in sulfoxidation reactions of L-methionine, N-acetyl-L-methionine and peptides containing L-methionine
Biochim. Biophys. Acta
1703
183-189
2005
Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus
Krueger, S.K.; Williams, D.E.
Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism
Pharmacol. Ther.
106
357-387
2005
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Sus scrofa
Mitchell, S.
Flavin mono-oxygenase (FMO) - The other oxidase
Curr. Drug Metab.
9
280-284
2008
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
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