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A52T
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
C530L
naturally occuring single nucleotide polymorphism of FMO2
D198E
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
D227K
pKa value 7.3 for N-oxygenation of 10-(N,N-dimethylaminooctyl)2-(trifluoromethyl)phenothiazene, compared with 6.9 for wild-type
D36G
naturally occuring single nucleotide polymorphism of FMO2
down
-
FMO5 is downregulated in type II diabetes in liver. FMO1 downregulation and inhibition by 3,3'-diindolylmethane
E132H
-
natural genetic variant of isozyme FMO2, substrate specificity, overview
E132H/E158K
-
natural genetic variant of isozyme FMO2, substrate specificity, overview
E158K/T201K/E308G
-
naturally occuring genetic variant of isozyme FMO3, and site-directed mutagenesis, the mutant shows reduced activity with sulindac and methyl 4-toyl sulfide compared to the wild-type FMO3
E158K/V257M
-
the naturally occuring polymorphisms reduce the oxidation and clearance of FMO3 substrates such as tyramine, and TMA in vitro, and mutations are highly likely to eliminate the enzyme function in vivo
E305X
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
E314G
naturally occuring single nucleotide polymorphism of FMO2
E314X
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
E32K
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
E339Q
naturally occuring single nucleotide polymorphism of FMO4
E362Q
naturally occuring single nucleotide polymorphism of FMO3
F182S
naturally occuring single nucleotide polymorphism of FMO2
F510X
-
natural genetic variant of isozyme FMO2, substrate specificity, overview
F69Y
naturally occuring single nucleotide polymorphism of FMO2
F81S
naturally occuring single nucleotide polymorphism of FMO2
G148X
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
G180V
naturally occuring single nucleotide polymorphism of FMO3, the mutant is similar to the wild-type enzyme
G182E
pKa value 6.6 for N-oxygenation of 10-(N,N-dimethylaminooctyl)2-(trifluoromethyl)phenothiazene, compared with 6.9 for wild-type
G475D
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
G503R
naturally occuring single nucleotide polymorphism of FMO3
H360P
-
site-directed mutagenesis of isozyme FMO1, the mutant shows altered thermal stability and highly increased activity with mercaptoimidazole and chlorpromazine compared to the wild-type FMO1
I199T
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
I468M
naturally occuring single nucleotide polymorphism of FMO3
K158L
-
Km-value for fenthion is 1.4fold higher than the wild-type value, Vmax for fenthion is nearly identical to the wild-type value, mutant of FMO3
K158L/D132H
-
Km-value for fenthion is 1.5fold higher than the wild-type value, Vmax for fenthion is 1.5fold higher than the wild-type value, mutant of FMO3
L360A
-
site-directed mutagenesis of isozyme FMO3, the mutant shows altered thermal stability and reduced activity with mercaptoimidazole, chlorpromazine, and 10-[(N,N-dimethylaminopentyl)-2-(trifluoromethyl)]phenothiazine compared to the wild-type FMO3
L360H
-
site-directed mutagenesis of isozyme FMO3, the mutant shows altered thermal stability and reduced activity with mercaptoimidazole, chlorpromazine, and 10-[(N,N-dimethylaminopentyl)-2-(trifluoromethyl)]phenothiazine compared to the wild-type FMO3
L360Q
-
site-directed mutagenesis of isozyme FMO3, the mutant shows altered thermal stability and reduced activity with mercaptoimidazole, chlorpromazine, and 10-[(N,N-dimethylaminopentyl)-2-(trifluoromethyl)]phenothiazine compared to the wild-type FMO3
M260V
naturally occuring single nucleotide polymorphism of FMO3
M434I
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
M82T
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
N114S
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
P457L
naturally occuring single nucleotide polymorphism of FMO4
Q170K
pKa value 6.6 for N-oxygenation of 10-(N,N-dimethylaminooctyl)2-(trifluoromethyl)phenothiazene, compared with 6.9 for wild-type
Q206H
pKa value 6.5 for N-oxygenation of 10-(N,N-dimethylaminooctyl)2-(trifluoromethyl)phenothiazene, compared with 6.9 for wild-type
Q470X
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
R238P
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
R238Q
naturally occuring single nucleotide polymorphism of FMO2
R249X
naturally occuring single nucleotide polymorphism of FMO2, probably inactive mutant
R378L
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
R391T
naturally occuring single nucleotide polymorphism of FMO2
R492W
-
naturally occuring mutation involved in trimethylaminuria, the mutant fails to incorporate/retain the FAD cofactor
R500X
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
R502V
-
no activity with methimazole, KM-value for methyl p-tolyl sulfide is 70% of the wild-type value, Vmax with methyl p-tolyl sulfide is 70% of the wild-type value, KM-value for imipramine is is nearly identical to the the wild-type value, Vmax with imipramine is 49% of the wild-type value, KM-value for fenthion is 88% of the wild-type value, Vmax with fenthion is 55% of wild-type value, mutant of FMO1
R506S
naturally occuring single nucleotide polymorphism of FMO4
R51G
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
T201K
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
T308S
naturally occuring single nucleotide polymorphism of FMO4
V143E
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
V257M/E308G
-
naturally occuring polymorphism, the substitutions do not affect enzyme activity in vitro
V257M/M260V
-
naturally occuring genetic variant of isozyme FMO3, and site-directed mutagenesis, the mutant shows reduced activity with sulindac and methyl 4-toyl sulfide compared to the wild-type FMO3
V277A
naturally occuring single nucleotide polymorphism of FMO3
V323A
naturally occuring single nucleotide polymorphism of FMO4
V58I
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
W388X
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
Y228H
pKa value 7.9 for N-oxygenation of 10-(N,N-dimethylaminooctyl)2-(trifluoromethyl)phenothiazene, compared with 6.9 for wild-type
E158A/E159A
-
the mutant shows similar activity with trimethylamine compared to the wild-type enzyme
Y207S
mutant exhibits very little indoxyl producing activity but the NADPH oxidase activity of the mutant is higher than that of the wild-type enzyme
E158A/E159A
-
the mutant shows similar activity with trimethylamine compared to the wild-type enzyme
-
Y207S
-
mutant exhibits very little indoxyl producing activity but the NADPH oxidase activity of the mutant is higher than that of the wild-type enzyme
-
C78A
-
site-directed mutagenesis, the mutation leads to an increase in KM and kcat compared to wild-type enzyme, but the mutant shows reduced activity compared to wild-type enzyme
C78I
-
site-directed mutagenesis, the mutation leads to an increase in KM and kcat compared to wild-type enzyme, but the mutant shows reduced activity compared to wild-type enzyme
C78L
-
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type enzyme
C78V
-
site-directed mutagenesis, the mutation leads to an increase in KM and kcat compared to wild-type enzyme, but the mutant shows reduced activity compared to wild-type enzyme
M15L/S23A
-
site-directed mutagenesis, combining the two mutations at the N-terminus results in a 3°C increase in apparent melting temperature. Both M15L and S23A are far from the active site and no significant effect on the kinetic parameters of the enzyme is observed. Adding more stabilizing mutations does not contribute to a higher thermostability
W319A
-
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type enzyme
W319F
-
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type enzyme
W47A
-
insoluble inactive protein
W47F
-
soluble and active protein. The spectrum of the flavin displays a redshift, the kcat values for NADPH, trimethylamine, and methimazole, show a 5-8fold decrease, and primary kinetic isotope effect values are higher than in wild-type. Mutant displays reduced flexibility in active site residues and, in particular, the nicotinamide moiety of NADP+
Y207W/W319A
-
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type enzyme
W47A
-
insoluble inactive protein
-
W47F
-
soluble and active protein. The spectrum of the flavin displays a redshift, the kcat values for NADPH, trimethylamine, and methimazole, show a 5-8fold decrease, and primary kinetic isotope effect values are higher than in wild-type. Mutant displays reduced flexibility in active site residues and, in particular, the nicotinamide moiety of NADP+
-
H228Y
pKa value 6.6 for N-oxygenation of 10-(N,N-dimethylaminooctyl)2-(trifluoromethyl)phenothiazene, compared with 7.7 for wild-type
K227D
pKa value 6.6 for N-oxygenation of 10-(N,N-dimethylaminooctyl)2-(trifluoromethyl)phenothiazene, compared with 7.7 for wild-type
D132H
-
KM-value and Vmax of fenthion are nearly identical to the wild-type values, mutant of FMO3
D132H
-
natural genetic variant of isozyme FMO2, substrate specificity, overview
D132H
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows substrate-dependent reduced activity
E158K
-
major naturally occuring structural varainat of isozyme FMO3, the mutant shows increased activity with tamoxifen compared to the wild-type enzyme
E158K
-
natural genetic variant of isozymes FMO2 and FMO3, substrate specificity, overview
E158K
-
naturally occuring genetic variant of isozyme FMO3, and site-directed mutagenesis, the mutant shows reduced activity with sulindac and methyl 4-toyl sulfide compared to the wild-type FMO3
E158K
-
naturally occuring polymorphism of FMO3, frequency in different human populations, the mutation has an impact on protein structure, overview
E158K
loss of function mutation of FMO3 results in trimethylaminuria or fish-odor-syndrome, the mutant enzyme is incapable of metabolizing trimethylamine to its non-odorous N-oxide, phenotype, overview
E158K
-
naturally occuring mutation not involved in primary trimethylaminuria
E158K
naturally occuring single nucleotide polymorphism of FMO3 in Europeans and Asians, the mutation slightly affects enzyme activity, substrate-dependent reduced activity, phenotype, overview
E158K
naturally occuring single nucleotide polymorphism of FMO3, the mutation slightly affects enzyme activity, substrate-dependent reduced activity
E158K
the mutant shows moderately reduced activity
E158K
naturally occuring mutation and site-directed mutagenesis, the mutant exhibits a significant increase in all the kinetic parameters measured with substrate tamoxifen with nearly two times faster clearance. The mutation has no effect on the clearance of GSK5182
E158K
naturally occuring polymorphic variant and site-directed mutagenesis, the melting temperature and activation energy of the mutant is nearly unaltered compared to the wild-type enzyme
E158K
naturally occuring polymorphism of FMO3, the E158K variant is mostly expressed in African-American and Europeans, the mutant shows reduced activity compared to the wild-type enzyme
E158K/E308G
-
natural genetic variant of isozyme FMO2, substrate specificity, overview
E158K/E308G
-
naturally occuring genetic variant of isozyme FMO3, and site-directed mutagenesis, the mutant shows reduced activity with sulindac and methyl 4-toyl sulfide compared to the wild-type FMO3
E158K/E308G
-
naturally occuring polymorphism, in many cases in vivo, altered clinical responses or altered susceptibility to various chemicals due to these sequence variants are observed compared to the carriers of at least one wild-type allele
E158K/E308G
-
naturally occuring mutation not involved in primary trimethylaminuria
E158K/E308G
naturally occuring single nucleotide polymorphism of FMO3 in Europeans and Asians, the mutation affects enzyme activity, substrate-dependent reduced activity, phenotype, overview
E158K/E308G
naturally occuring single nucleotide polymorphism of FMO3, the mutation affects enzyme activity, substrate-dependent reduced activity
E24D
-
naturally occuring polymorphism of FMO3, frequency in different human populations, the mutation has an impact on protein structure, overview, the mutant shows altered substrate specificity compared to the wild-type mutant
E24D
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows reduced activity
E308G
-
natural genetic variant of isozyme FMO2, substrate specificity, overview
E308G
-
naturally occuring polymorphism of FMO3, frequency in different human populations, the mutation has an impact on protein structure, overview
E308G
loss of function mutation of FMO3 results in trimethylaminuria or fish-odor-syndrome, the mutant enzyme is incapable of metabolizing trimethylamine to its non-odorous N-oxide, phenotype, overview
E308G
-
naturally occuring mutation not involved in primary trimethylaminuria
E308G
naturally occuring single nucleotide polymorphism of FMO3 in Europeans and Asians, the mutation slightly affects enzyme activity, substrate-dependent reduced activity, phenotype, overview
E308G
naturally occuring single nucleotide polymorphism of FMO3, the mutation slightly affects enzyme activity, substrate-dependent reduced activity
E308G
the mutant shows moderately reduced activity
E308G
naturally occuring mutation and site-directed mutagenesis, the mutant exhibits a significant increase in all the kinetic parameters measured with substrate clomiphene with nearly two times faster clearance. The mutation has no effect on the clearance of GSK5182
E308G
naturally occuring polymorphic variant and site-directed mutagenesis, the mutant is unable to bind the NADP+ cofactor, it shows a significantly higher energy of unfolding (Ea) compared to wild-type
E308G
naturally occuring polymorphism of FMO3, the E308G is widely distributed in Asians and Europeans, the mutant shows reduced activity compared to the wild-type enzyme
H97Q
-
KM-value for methimazole is 3fold higher than wild-type value, Vmax with methimazole is 1.6fold higher than the wild-type value, KM-value for methyl p-tolyl sulfide is 88% of the wild-type value, Vmax with methyl p-tolyl sulfide is 1.4fold higher than the wild-type value, KM-value for imipramine is is nearly identical to the the wild-type value, Vmax with imipramine is 1.3fold higher than the wild-type value, KM-value for fenthion is 94% of the wild-type value, Vmax with fenthion is 1.3fold higher than the wild-type value, mutant of FMO1
H97Q
-
natural genetic variant of isozyme FMO1, substrate specificity, overview
H97Q
naturally occuring single nucleotide polymorphism of FMO1, the mutant enzyme is similar to the wild-type enzyme
I303T
-
KM-value for methimazole is 2.3fold higher than wild-type value, Vmax with methimazole is 1.8fold higher than the wild-type value, KM-value for methyl p-tolyl sulfide is 86% of the wild-type value, Vmax with methyl p-tolyl sulfide is 1.8fold higher than the wild-type value, KM-value for imipramine is identical to the the wild-type value, Vmax with imipramine is 1.4fold higher than the wild-type value, KM-value for fenthion is 94% of the wild-type value, Vmax with fenthion is 1.6fold higher than the wild-type value, mutant of FMO1
I303T
-
natural genetic variant of isozyme FMO1, substrate specificity, overview
I303T
naturally occuring single nucleotide polymorphism of FMO1, the mutant enzyme is similar to the wild-type enzyme
I303V
-
KM-value for methimazole is identical to the wild-type value, Vmax with methimazole is nearly identical to the wild-type value, KM-value and Vmax for meth is 1,4fold higher than the the wild-type value, Vmax with imipramine is nearly identical to the wild-type value, KM-value and Vmax for fenthion are nearly identical to the wild-type values, mutant of FMO1
I303V
-
natural genetic variant of isozyme FMO1, substrate specificity, overview
I303V
naturally occuring single nucleotide polymorphism of FMO1, the mutant enzyme is similar to the wild-type enzyme
I37T
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
I37T
naturally occuring single nucleotide polymorphism of FMO4
K416N
-
naturally occuring polymorphism of FMO3, frequency in different human populations, the mutation has an impact on protein structure, overview, the mutant shows altered substrate specificity compared to the wild-type mutant
K416N
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows reduced activity
L360P
-
natural genetic variant of isozyme FMO2, substrate specificity, overview
L360P
-
site-directed mutagenesis of isozyme FMO3, the mutant shows altered thermal stability and increased activity with mercaptoimidazole, chlorpromazine, and 10-[(N,N-dimethylaminopentyl)-2-(trifluoromethyl)]phenothiazine compared to the wild-type FMO3
L360P
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows increased activity
L360P
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows increased activity
L360P
the mutation increases catalytic activity
M66I
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
M66I
-
naturally occuring mutation involved in trimethylaminuria, the mutant fails to incorporate/retain the FAD cofactor
N413K
naturally occuring single nucleotide polymorphism of FMO2, the mutant is similar to the wild-type enzyme
N413K
naturally occuring mutant of the FMO2*1 allele, the mutant shows higher kcat and Vmax, and increased thermosensitivity compared to the wild-type enzyme, activity is stabilized by NADPH
N413K
-
the mutant of isoform FMO2 exhibits higher catalytic activity toward methyl-4-tolyl sulfide compared to the wild type enzyme
N61K
-
naturally occuring polymorphism of FMO3, frequency in different human populations, the mutation has an impact on protein structure, overview, the mutant shows altered substrate specificity compared to the wild-type mutant
N61K
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows reduced activity
N61K
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows reduced activity
N61S
loss of function mutation of FMO3 results in trimethylaminuria or fish-odor-syndrome, the mutant enzyme is incapable of metabolizing trimethylamine to its non-odorous N-oxide, nuta this mutant is still active with methimazole, phenotype, overview
N61S
loss of function mutation of FMO3 results in trimethylaminuria or fish-odor-syndrome, the mutant enzyme is incapable of metabolizing trimethylamine to its non-odorous N-oxide, nuta this mutant is still active with methimazole, phenotype, overview
N61S
-
naturally occuring mutation involved in trimethylaminuria, the mutant shows over 90% reduced activity with trimethylamine compared to the wild-type enzyme
N61S
an active site polymorphic variant, the single-nucleotide polymorphism is leading to deleterious effects of oxidative stress. N-Oxygenation of benzydamine by the wild-type and N61S mutant variant of FMO3. In the absence of the substrate benzydamine (BZD), N61S produces higher amounts of H2O2 compared to wild-type
P153L
loss of function mutation of FMO3 results in trimethylaminuria or fish-odor-syndrome, the mutant enzyme is incapable of metabolizing trimethylamine to its non-odorous N-oxide, phenotype, overview
P153L
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
P153L
-
naturally occuring mutation involved in trimethylaminuria, the mutant shows over 90% reduced activity with trimethylamine compared to the wild-type enzyme
Q472X
naturally occuring single nucleotide polymorphism of FMO2, inactive mutant
Q472X
naturally occuring single nucleotide polymorphism of FMO2, inactive mutant
Q472X
naturally occuring mutant of the FMO2*1 allele, more frequent in the sub-Sahara African population
R205C
-
naturally occuring genetic variant of isozyme FMO3, and site-directed mutagenesis, the mutant shows reduced activity with sulindac and methyl 4-toyl sulfide compared to the wild-type FMO3, and is almost substrate inhibited, wild-type FMO3 has no free cysteine residues in the native form
R205C
loss of function mutation of FMO3 results in trimethylaminuria or fish-odor-syndrome, the mutant enzyme is incapable of metabolizing trimethylamine to its non-odorous N-oxide, phenotype, overview
R205C
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows highly reduced activity
R205C
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows reduced activity
R223Q
naturally occuring mutation causing trimethylaminuria or fish-odor-syndrome
R223Q
naturally occuring single nucleotide polymorphism of FMO1
R502X
-
natural genetic variant of isozyme FMO1, substrate specificity, overview
R502X
naturally occuring single nucleotide polymorphism of FMO1, the mutant shows substrate-dependent reduced activity compared to the wild-type enzyme
R502X
naturally occuring single nucleotide polymorphism of FMO1, the mutant shows substrate-dependent reduced activity compared to the wild-type enzyme
S195L
naturally occuring single nucleotide polymorphism of FMO2, inactive mutant
S195L
naturally occuring mutant of the FMO2*1 allele, the mutant shows reduced activity and increased pH sensitivity and thermosensitivity compared to the wild-type enzyme, activity is stabilized by NADPH
S195L
-
the mutant of isoform FMO2 exhibits lower catalytic activity toward methyl-4-tolyl sulfide and ethylene thiourea compared to the wild type enzyme
V257M
-
variant with 13.21% allele frequency. Mutation causes a transformation of the secondary structure. The presence of this mutant allele correlates significantly with a reduction in caffeine N-1-demethylating activity
V257M
-
natural genetic variant of isozyme FMO3, substrate specificity, overview
V257M
-
naturally occuring genetic variant of isozyme FMO3, and site-directed mutagenesis, the mutant shows reduced activity with sulindac and methyl 4-toyl sulfide compared to the wild-type FMO3
V257M
loss of function mutation of FMO3 results in trimethylaminuria or fish-odor-syndrome, the mutant enzyme is incapable of metabolizing trimethylamine to its non-odorous N-oxide, phenotype, overview
V257M
-
naturally occuring mutation not involved in primary trimethylaminuria
V257M
naturally occuring single nucleotide polymorphism of FMO3, the mutant shows slightly reduced activity
V257M
naturally occuring mutation and site-directed mutagenesis, residue V257 is not in the immediate vicinity of the active site and is part of the hFMO3 insert region in a loop that protrudes from the NADP+-binding domain across the FAD-binding domain, the mutant exhibits a significant increase in all the kinetic parameters measured with substrate clomiphene with nearly two times faster clearance, while the clearance with substrate tamoxifen is reduced. The mutation has no effect on the clearance of GSK5182
V257M
naturally occuring polymorphic variant and site-directed mutagenesis, the melting temperature and activation energy of the mutant is nearly unaltered compared to the wild-type enzyme
V257M
naturally occuring polymorphism of FMO3, the V257M polymorphic variant is predominantly present in Asians, the mutant shows reduced activity compared to the wild-type enzyme
Y207W
-
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type enzyme
Y207W
-
site-directed mutagenesis, the mutation leads to an increase in KM and kcat, as well as in catalytic efficiency, compared to wild-type enzyme
additional information
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an Arabidopsis FMO1 knockout line is fully impaired in the establishment of systemic acquired resistance, SAR, triggered by virulent bacteria, loss of SAR in the FMO1 mutants is accompanied by the inability to initiate systemic accumulation of salicylic acid and systemic expression of diverse defense related genes, overview, fmo1mutation does not significantly affect local disease resistance toward virulent or avirulent bacteria in native plants
additional information
construction of fmo1 defective mutants, FMO1 mutations specifically affects the EDS1 pathway, defects in Arabidopsis fmo1 mutants are not coupled to SA accumulation, reduced pathogen defense, phenotype, analysis of fmo1 and nudt7 mutants alone or in combination with sid2-1, a mutation that severely depletes pathogen-induced salicylic acid production, points to salicylic acid-independent functions of FMO1 and NUDT7 in EDS1-conditioned disease resistance and cell death, overview
additional information
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construction of fmo1 defective mutants, FMO1 mutations specifically affects the EDS1 pathway, defects in Arabidopsis fmo1 mutants are not coupled to SA accumulation, reduced pathogen defense, phenotype, analysis of fmo1 and nudt7 mutants alone or in combination with sid2-1, a mutation that severely depletes pathogen-induced salicylic acid production, points to salicylic acid-independent functions of FMO1 and NUDT7 in EDS1-conditioned disease resistance and cell death, overview
additional information
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isolation of a dominant, gain-of-function phenotype FMO1-3D mutant, insertion at At1g19260 and towards the At1g19250 locus, from Arabidopsis thaliana, using activation tagging in the Arabidopsis Col-0 rps2-101C background, the mutant shows virtually no symptoms after inoculation with virulent Pseudomonas syringae pv. tomato DC3000 bacteria and downy mildew-causing pathogen Hyaloperonospora parasitica due to overexpression of class 3 FMO, overview, overexpression of the FMO1 cDNA, under control of the 35S CaMV promoter in independent transgenic Col-0 lines, leads to the same phenotype, progeny from crosses of the FMO1-3D mutant with the NahG transgenic line show that the enhanced basal resistance phenotype is dependent on the accumulation of salicylic acid, the R-gene-mediated defence physiology is not compromised by FMO1 overexpression, T-DNA insertion into the FMO1 gene resulted in enhances the susceptibility to virulent Pseudomonas and Hyaloperonospora parasitica, phenotypes, overview
additional information
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determination and analysis of frequencies of 18 FMO3 single-nucleotide polymorphisms in 202 Hispanics of Mexican descent, 201 African Americans, and 200 non-Latino whites, synonymous mutations, and hypomorphic haplotypes, overview
additional information
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effects of genetic variants of isozyme FMO3 on N- and S-oxygenation activities, genotype-phenotype studies, overview
additional information
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identification and analysis of 18 mutations of FMO3 genes from 134 AfricanAmericans and 129 Caucasians from the United States, missense and nonsense nucleotide substitutions, and polymorphic variants of the gene, both involved in development of trimethylaminuria, TMAU, interindividual variability in the expression of FMO3 may affect drug and exogenous chemical metabolism in the liver and other tissues, clinical relevance of the polymorphisms, overview
additional information
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occuring single nucleotide polymorphisms are associated with dramatic functional differences in selective functional enzyme activity, overview
additional information
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three of the five expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms, overview
additional information
FMO3 is highly polymorphic, with as many as 15 nonsynonymous single nucleotide polymorphisms identified, many of which are present at relatively high frequency, several single nucleotide polymorphisms cause loss of function mutation of FMO3 resulting in trimethylaminuria or fish-odor-syndrome, the mutant enzymes are incapable of metabolizing trimethylamine to its non-odorous N-oxide, haplotypes and phenotypes, overview
additional information
FMO3 is highly polymorphic, with as many as 15 nonsynonymous single nucleotide polymorphisms identified, many of which are present at relatively high frequency, several single nucleotide polymorphisms cause loss of function mutation of FMO3 resulting in trimethylaminuria or fish-odor-syndrome, the mutant enzymes are incapable of metabolizing trimethylamine to its non-odorous N-oxide, haplotypes and phenotypes, overview
additional information
FMO3 is highly polymorphic, with as many as 15 nonsynonymous single nucleotide polymorphisms identified, many of which are present at relatively high frequency, several single nucleotide polymorphisms cause loss of function mutation of FMO3 resulting in trimethylaminuria or fish-odor-syndrome, the mutant enzymes are incapable of metabolizing trimethylamine to its non-odorous N-oxide, haplotypes and phenotypes, overview
additional information
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FMO3 is highly polymorphic, with as many as 15 nonsynonymous single nucleotide polymorphisms identified, many of which are present at relatively high frequency, several single nucleotide polymorphisms cause loss of function mutation of FMO3 resulting in trimethylaminuria or fish-odor-syndrome, the mutant enzymes are incapable of metabolizing trimethylamine to its non-odorous N-oxide, haplotypes and phenotypes, overview
additional information
genotyping of FMO3 in a Japanese cohort, missense and nonsense mutations, overview
additional information
most humans are homozygous for a nonsense mutation that inactivates FMO2. But a substantial proportion of sub-Saharan Africans express functional FMO2 and, thus, are predicted to respond differently to drugs and other foreign chemicals
additional information
most humans are homozygous for a nonsense mutation that inactivates FMO2. But a substantial proportion of sub-Saharan Africans express functional FMO2 and, thus, are predicted to respond differently to drugs and other foreign chemicals
additional information
most humans are homozygous for a nonsense mutation that inactivates FMO2. But a substantial proportion of sub-Saharan Africans express functional FMO2 and, thus, are predicted to respond differently to drugs and other foreign chemicals
additional information
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most humans are homozygous for a nonsense mutation that inactivates FMO2. But a substantial proportion of sub-Saharan Africans express functional FMO2 and, thus, are predicted to respond differently to drugs and other foreign chemicals
additional information
naturally occuring mutations, including silent mutations, genotyping, overview
additional information
naturally occuring mutations, including silent mutations, genotyping, overview
additional information
naturally occuring mutations, including silent mutations, genotyping, overview
additional information
naturally occuring mutations, including silent mutations, genotyping, overview
additional information
naturally occuring mutations, including silent mutations, genotyping, overview
additional information
several single nucleotide polymorphisms cause loss of function mutation of FMO3 resulting in trimethylaminuria or fish-odor-syndrome, the mutant enzymes are incapable of metabolizing trimethylamine to its non-odorous N-oxide, haplotypes and phenotypes, overview
additional information
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several single nucleotide polymorphisms cause loss of function mutation of FMO3 resulting in trimethylaminuria or fish-odor-syndrome, the mutant enzymes are incapable of metabolizing trimethylamine to its non-odorous N-oxide, haplotypes and phenotypes, overview
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the HepG2 model is suitable for the study of FMO3 regulation, deletion analysis of FMO3/luciferase reporter constructs, domains A-I, and specific transcription factor responsive elements identified by DNA-protein binding reactions and site-directed mutagenesis of FMO3 reporter constructs, functional analysis of the FMO3 HNF3, and C/EBP elements, FMO3 promoter analysis, overview
additional information
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the HepG2 model is suitable for the study of FMO3 regulation, deletion analysis of FMO3/luciferase reporter constructs, domains A-I, and specific transcription factor responsive elements identified by DNA-protein binding reactions and site-directed mutagenesis of FMO3 reporter constructs, functional analysis of the FMO3 HNF3, and C/EBP elements, FMO3 promoter analysis, overview
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enzyme activity analysis using a simple but functional and stable enzyme-electrode system based on a glassy carbon electrode with human flavin-containing monooxygenase isoform 3 entrapped in a gel cross-linked with bovine serum albumin by glutaraldehyde, method development and evaluation, overview
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generation of humanized-liver TK-NOG mice, chimeric mice, in which more than 90% of liver cells are estimated to have been replaced with human hepatocytes, interactions between FMO substrates in humanized-liver mice, overview. Administered itopride (10 mg/kg) is extensively oxygenated to its N-oxide in humanized-liver mouse plasma. The area under the concentration-time curve of itopride N-oxide is 15fold that of itopride in humanize-liver mice
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generation of truncated forms of wild-type and mutant enzymes, the 17 amino acid truncation at the C-terminal of FMO3 results in a more soluble protein, the truncated enzymes are better catalysts than the full-length proteins. The truncated enzymes are not only fully active, but also have a higher vmax compared to their full-length counterparts, the latter observation might be the result of their higher solubility. The mutations have no major effect on the interaction of the FAD cofactor with the protein
additional information
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generation of truncated forms of wild-type and mutant enzymes, the 17 amino acid truncation at the C-terminal of FMO3 results in a more soluble protein, the truncated enzymes are better catalysts than the full-length proteins. The truncated enzymes are not only fully active, but also have a higher vmax compared to their full-length counterparts, the latter observation might be the result of their higher solubility. The mutations have no major effect on the interaction of the FAD cofactor with the protein
additional information
unfolding process of a phase I drug metabolizing enzyme, human flavin-containing monooxygenase 3 (hFMO3) and its single nucleotide polymorphic variants (SNPs) V257M, E158K and E308G are analyzed by differential scanning calorimetry (DSC) indicating that the thermal denaturation of the enzyme is irreversible. The melting temperature (Tm) for the wild-type enzyme and its polymorphic variants is in a range from 46°C to 50°C. Also the activation energies of unfolding (Ea) show no significant differences among all proteins investigated (290-328 KJ/mol), except for the E308G variant that shows a significantly higher Ea of 412 KJ/mol. The presence of the bound NADP+ cofactor stabilizes all the variants by shifting the main Tm by 4-5°C for all the proteins, exception made for E308G where no changes are observed
additional information
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unfolding process of a phase I drug metabolizing enzyme, human flavin-containing monooxygenase 3 (hFMO3) and its single nucleotide polymorphic variants (SNPs) V257M, E158K and E308G are analyzed by differential scanning calorimetry (DSC) indicating that the thermal denaturation of the enzyme is irreversible. The melting temperature (Tm) for the wild-type enzyme and its polymorphic variants is in a range from 46°C to 50°C. Also the activation energies of unfolding (Ea) show no significant differences among all proteins investigated (290-328 KJ/mol), except for the E308G variant that shows a significantly higher Ea of 412 KJ/mol. The presence of the bound NADP+ cofactor stabilizes all the variants by shifting the main Tm by 4-5°C for all the proteins, exception made for E308G where no changes are observed
additional information
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preparation of self-sufficient monooxygenases by covalent coupling of mFMO with the soluble NADPHregenerating phosphite dehydrogenase, PTDH, from Pseudomonas stutzeri using a codon-optimized gene encoding a His-tagged and thermostable PTDH mutant as fusion partner. The bifunctional biocatalyst is able to use phosphite as a cheap and sacrificial substrate for recycling NADPH
additional information
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preparation of self-sufficient monooxygenases by covalent coupling of mFMO with the soluble NADPHregenerating phosphite dehydrogenase, PTDH, from Pseudomonas stutzeri using a codon-optimized gene encoding a His-tagged and thermostable PTDH mutant as fusion partner. The bifunctional biocatalyst is able to use phosphite as a cheap and sacrificial substrate for recycling NADPH
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construction of Fmo1-/-, 2-/-, and 4-/- knockout mutants, 1D 1H NMR spectroscopy to compare the urinary metabolite profiles of the knockout-mouse line and wild-type animals, metabolic profiles of hypotaurine and taurine in wild-type and mutant mice' urine samples, overview
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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
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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