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Information on EC 1.14.14.B11 - nicotine demethylase
for references in articles please use BRENDA:EC1.14.14.B11
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Old data from external sources may still be available.
Please check here for current data: EC unknown
Please check here for current data: EC unknown
preliminary BRENDA-supplied EC number
EC Tree 1 Oxidoreductases
1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen
1.14.14 With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
1.14.14.B11 nicotine demethylase
The enzyme appears in viruses and cellular organisms
- 1.14.14.B11
- nornicotine
- nicotiana
- tabacum
-
n-demethylation
- n'-nitrosonornicotine
-
tobacco-specific
-
nitrosamine
-
burley
- demethylases
- tomentosiformis
-
curing
- sylvestris
-
s-nicotine
-
nonconverter
- nutrition
-
rnai-induced
-
elicitor-induced
- agriculture
Reaction Schemes
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Synonyms
cyp82e4, nicotine n-demethylase, cyp82e, nicotine demethylase, cyp82e5v2, cyp82e10, cyp82e21, cyp82e1, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CYP82E
CYP82E1
CYP82E10
CYP82E2
CYP82E4
CYP82E5v2
nicotine N-demethylase
NND
CYP82E2
-
-
-
-
CYP82E4
-
-
-
-
CYP82E5v2
-
-
-
-
nicotine N-demethylase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(R)-nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2 = (R)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2 = (S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
nicotine,[NADPH-hemoprotein reductase]:oxygen oxidoreductase (demethylating)
-
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CAS REGISTRY NUMBER
COMMENTARY
97162-77-1
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(R)-nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2
(R)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: isoforms CYP82E4, CYP82E5v2, and CYP82E10 demethylate (R)-nicotine 3, 10, and 10fold faster than (S)-nicotine, respectively
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
additional information
?
-
-
Substrates: isoforms CYP2A6 and CYP2B6 significantly contribute to the nicotine N-demethylation at low and high substrate concentrations, respectively
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: CYP82E4 selectively demethylates (S)-nicotine
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: only isoform CYP82E4 can significantly convert (S)-nicotine to (S)-nornicotine
Products: -
Products: -
?
nicotine + NADPH + H+
nornicotine + NADP+
Q38Q86
Substrates: -
Products: -
Products: -
?
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
Substrates: demethylates nicotine to form nornicotine, a precursor to the nitrosamine N'-nitrosonornicotine
Products: -
Products: -
?
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
Substrates: -
Products: -
Products: -
?
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
Substrates: six putative substrate recognition sites
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
Substrates: -
Products: isoform CYP82E4v1 is responsible for the conversion of nicotine to nornicotine
Products: isoform CYP82E4v1 is responsible for the conversion of nicotine to nornicotine
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
Substrates: nornicotine is a secondary tobacco alkaloid that is produced by the N-demethylation of nicotine. Nornicotine production and accumulation in tobacco are undesirable because nornicotine serves as the precursor in the synthesis of the carcinogen N-nitrosonornicotine during the curing and processing of tobacco
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(R)-nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2
(R)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: isoforms CYP82E4, CYP82E5v2, and CYP82E10 demethylate (R)-nicotine 3, 10, and 10fold faster than (S)-nicotine, respectively
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
Substrates: demethylates nicotine to form nornicotine, a precursor to the nitrosamine N'-nitrosonornicotine
Products: -
Products: -
?
nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: CYP82E4 selectively demethylates (S)-nicotine
Products: -
Products: -
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
Substrates: only isoform CYP82E4 can significantly convert (S)-nicotine to (S)-nornicotine
Products: -
Products: -
?
nicotine + NADPH + H+
nornicotine + NADP+
Q38Q86
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
Substrates: -
Products: isoform CYP82E4v1 is responsible for the conversion of nicotine to nornicotine
Products: isoform CYP82E4v1 is responsible for the conversion of nicotine to nornicotine
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
Substrates: nornicotine is a secondary tobacco alkaloid that is produced by the N-demethylation of nicotine. Nornicotine production and accumulation in tobacco are undesirable because nornicotine serves as the precursor in the synthesis of the carcinogen N-nitrosonornicotine during the curing and processing of tobacco
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
Substrates: -
Products: -
Products: -
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Substrates: -
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Chloropromazine
1 mM, 87% inhibition of recombinant nicotine demethylase activity in yeast microsomes
cytochrome c
1 mM, 78% inhibition of recombinant nicotine demethylase activity in yeast microsomes
additional information
-
not inhibitory: quinidine, anti-CYP2D6 serum, ketoconazole, anti-CYP3A4 serum
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no activiation by putrescine, glycine, or ethanolamine
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Virus Diseases
CYP82E4-mediated nicotine to nornicotine conversion in tobacco is regulated by a senescence-specific signaling pathway.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0203
(S)-nicotine
isoform CYP82E1, in 50 mM Tris-HCl (pH 7.5), at 25°C
0.054
(S)-nicotine
isoform CYP82E2, in 50 mM Tris-HCl (pH 7.5), at 25°C
0.0619
(S)-nicotine
isoform CYP82E4, in 50 mM Tris-HCl (pH 7.5), at 25°C
0.0684
(S)-nicotine
isoform CYP82E1, in 50 mM Tris-HCl (pH 7.5), at 25°C
0.1186
(S)-nicotine
isoform CYP82E3, in 50 mM Tris-HCl (pH 7.5), at 25°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
regarding sepals, petals, ovaries, stigma including style, filaments and anthers, CYP82E21 expression is found almost exclusively in ovaries, with very low expression levels observed in other flower organs
brenda
-
nicotine N-demethylase activity in microsomes from human livers at 0.02 mM nicotine is significantly correlated with the isoform CYP2A6 contents, while the nicotine N-demethylase activity at 0.1 mM nicotine is significantly correlated with the isoform CYP2B6 contents
brenda
additional information
-
CYP82E21 expression pattern analysis, CYP82E21 is specifically expressed in ovaries but not expressed in leaves
brenda
induced in leaves treated with the growth regulator ethylene
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
putative N-terminal hydrophobic trans-membrane domain
brenda
-
nicotine N-demethylase activity in microsomes from human livers at 0.02 mM nicotine is significantly correlated with the isoform CYP2A6 contents, while the nicotine N-demethylase activity at 0.1 mM nicotine is significantly correlated with the isoform CYP2B6 contents
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
N-demethylase enzymes (NND) belongs to the family of cytochrome P450 monooxygenases (CYP). The CYP82E21 gene is found in all Nicotiana tabacum cultivars analysed and originates from the tobacco ancestor Nicotiana tomentosiformis
malfunction
metabolism
four NND genes mediating nicotine to nornicotine conversion have been cloned from burley tobacco: CYP82E4, CYP82E5, CYP82E10, and CYP82E21. CYP82E21 encodes an active demethylase, but it is only expressed in the ovary and may contribute little to nornicotine formation
physiological function
malfunction
-
nornicotine formation can be reduced in ovaries by introducing a CYP82E21-specific RNAi construct
malfunction
Q38Q86
RNA interference of the nicotine demethylase gene CYP82E4v1 reduces nornicotine content and enhances Myzus persicae resistance in Nicotiana tabacum infected with aphids
malfunction
the nicotine to nornicotine conversion rate (NCR) in a mutant of CYP82E4 (e4/e4/E5E5/E10E10) is about 2.2% and is much lower than that in control plants, indicating that CYP82E4 is the major NND for nicotine demethylation in burley tobacco. Consistent with this observation, no significant difference is found between single mutant of CYP82E10 (E4E4/E5E5/e10e10), a double mutant of CYP82E5 and CYP82E10 (E4E4/e5e5/e10e10), and control plants. But introducing the e5e5e10e10 mutation into the e4e4 background results in even lower conversion rate, indicating minor roles for CYP82E5 and CYP82E10
physiological function
only microsomes from yeast expressing the D121-AA8 cDNA exhibit significant nicotine demethylase activity
physiological function
-
the CYP82E21 gene encodes a functional ovary-specific nicotine N-demethylase, nornicotine is formed by oxidative demethylation of nicotine
physiological function
the nicotine N-demethylase (NND) is involved in formation of nornicotine, which is the precursor of the carcinogen N-nitrosonornicotine (NNN)
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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). A9QNE6_TOBAC
517
0
59402
TrEMBL
other Location (Reliability: 3)
E5G962_TOBAC
517
0
59461
TrEMBL
Mitochondrion (Reliability: 4)
J7M5N9_NICAL
514
0
58904
TrEMBL
Secretory Pathway (Reliability: 1)
J7M8Q0_NICLA
516
0
59177
TrEMBL
other Location (Reliability: 1)
J7MB22_NICAL
514
0
58973
TrEMBL
other Location (Reliability: 2)
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C330W
K269N/I274Null
isoform CYP82E3 variant, no catalytic activity
K269N/I274Null/T279A
isoform CYP82E3 variant, no catalytic activity
additional information
additional information
analysis of polymorphic variations of the CYP82E2 orthologs in Nicotiana sylvestris and various Nicotiana tabacum genotypes
additional information
-
analysis of polymorphic variations of the CYP82E2 orthologs in Nicotiana sylvestris and various Nicotiana tabacum genotypes
additional information
-
inhibition of gene expression by RNAi leads to up ot sixfold decrease in nornicotine content with concomitant decrease in N'-nitrosonornicotine and total tobacco-specific nitrosamines
additional information
-
while the nornicotine content of most commercial burley tobacco is low, a process termed conversion can bestow considerably increased nornicotine levels in a portion of the plants within the population. Transcript accumulation of isoform CYP82E4 is enhanced as much as 80fold in converter vs nonconverter tobacco. An optimized RNAi construct 82E4Ri298 suppresses nicotine to nornicotine conversion from 98% to as low as 0.8% in a strong converter tobacco line, a rate of nornicotine production that is about 3.6fold lower than typically detected in commercial varieties. Greenhouse-grown transgenic plants transformed with the RNAi construct are morphologically indistinguishable from the empty vector or wild-type controls
additional information
-
wild-type isoform CYP82E3 shares 95% predicted amino acid sequence identity with isoform CYP82E4 but conferrs no activity when expressed in yeast or tobacco. Series of domain-swapping experiments between isoforms CYP82E3 and CYP82E4 to isentify regions and amino acids required for catalytic activity
additional information
-
enzyme silencing by introducing a CYP82E21-specific RNAi construct in ovaries, silencing of CYP82E21 leads to up to 90% reduced nicotine conversion in flower ovaries
additional information
Q38Q86
enzyme silencing by CYP82E21-specific RNAi expression. CYP82E4v1-interference affects the accumulation of nicotine and nornicotine, and the RNAi vector for CYP82E4v1 effectively silences CYP82E4v1 expression and further blocks the synthesis of nornicotine
additional information
-
enzyme silencing by CYP82E21-specific RNAi expression. CYP82E4v1-interference affects the accumulation of nicotine and nornicotine, and the RNAi vector for CYP82E4v1 effectively silences CYP82E4v1 expression and further blocks the synthesis of nornicotine
additional information
generation of wild-type enzymes, homozygous mutants, and heterozygous mutants (marked as A/A, a/a and A/a, respectively), the nicotine to nornicotine conversion rate (NCR) in a mutant of CYP82E4 (e4/e4/E5E5/E10E10) is about 2.2% and is much lower than that in control plants, indicating that CYP82E4 is the major NND for nicotine demethylation in burley tobacco. Consistent with this observation, no significant difference is found between single mutant of CYP82E10 (E4E4/E5E5/e10e10), a double mutant of CYP82E5 and CYP82E10 (E4E4/e5e5/e10e10), and control plants. But introducing the e5e5e10e10 mutation into the e4e4 background results in even lower conversion rate, indicating minor roles for CYP82E5 and CYP82E10
additional information
generation of wild-type enzymes, homozygous mutants, and heterozygous mutants (marked as A/A, a/a and A/a, respectively), the nicotine to nornicotine conversion rate (NCR) in a mutant of CYP82E4 (e4/e4/E5E5/E10E10) is about 2.2% and is much lower than that in control plants, indicating that CYP82E4 is the major NND for nicotine demethylation in burley tobacco. Consistent with this observation, no significant difference is found between single mutant of CYP82E10 (E4E4/E5E5/e10e10), a double mutant of CYP82E5 and CYP82E10 (E4E4/e5e5/e10e10), and control plants. But introducing the e5e5e10e10 mutation into the e4e4 background results in even lower conversion rate, indicating minor roles for CYP82E5 and CYP82E10
additional information
generation of wild-type enzymes, homozygous mutants, and heterozygous mutants (marked as A/A, a/a and A/a, respectively), the nicotine to nornicotine conversion rate (NCR) in a mutant of CYP82E4 (e4/e4/E5E5/E10E10) is about 2.2% and is much lower than that in control plants, indicating that CYP82E4 is the major NND for nicotine demethylation in burley tobacco. Consistent with this observation, no significant difference is found between single mutant of CYP82E10 (E4E4/E5E5/e10e10), a double mutant of CYP82E5 and CYP82E10 (E4E4/e5e5/e10e10), and control plants. But introducing the e5e5e10e10 mutation into the e4e4 background results in even lower conversion rate, indicating minor roles for CYP82E5 and CYP82E10
additional information
wild-type isoform CYP82E3 shares 95% predicted amino acid sequence identity with isoform CYP82E4 but confers no activity when expressed in yeast or tobacco. Series of domain-swapping experiments between isoforms CYP82E3 and CYP82E4 to isentify regions and amino acids required for catalytic activity
additional information
wild-type isoform CYP82E3 shares 95% predicted amino acid sequence identity with isoform CYP82E4 but confers no activity when expressed in yeast or tobacco. Series of domain-swapping experiments between isoforms CYP82E3 and CYP82E4 to isentify regions and amino acids required for catalytic activity
additional information
-
wild-type isoform CYP82E3 shares 95% predicted amino acid sequence identity with isoform CYP82E4 but confers no activity when expressed in yeast or tobacco. Series of domain-swapping experiments between isoforms CYP82E3 and CYP82E4 to isentify regions and amino acids required for catalytic activity
additional information
wild-type isoform CYP82E3 shares 95% predicted amino acid sequence identity with isoform CYP82E4 but confers no activity when expressed in yeast or tobacco. Series of domain-swapping experiments between isoforms CYP82E3 and CYP82E4 to identify regions and amino acids required for catalytic activity
additional information
wild-type isoform CYP82E3 shares 95% predicted amino acid sequence identity with isoform CYP82E4 but confers no activity when expressed in yeast or tobacco. Series of domain-swapping experiments between isoforms CYP82E3 and CYP82E4 to identify regions and amino acids required for catalytic activity
additional information
-
wild-type isoform CYP82E3 shares 95% predicted amino acid sequence identity with isoform CYP82E4 but confers no activity when expressed in yeast or tobacco. Series of domain-swapping experiments between isoforms CYP82E3 and CYP82E4 to identify regions and amino acids required for catalytic activity
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Saccharomyces cerevisiae
gene CYP82E10, DNA and amino acid sequence determination and analysis, phylogenetic analysis, quantitative RT-PCR enzyme expression analysis
gene CYP82E21, unrooted phylogenetic analysis and tree of CYP82E21 and related CYP82E coding sequences, quantitative PCR enzyme expression analysis, ectopic expression of the coding sequence in a tobacco line lacking functional CYP82E4, CYP82E5 and CYP82E10 genes, resulting in an eightfold increase of nicotine demethylation compared to the control plants confirming the nicotine N-demethylase activity of CYP82E21
-
gene CYP82E4, DNA and amino acid sequence determination and analysis, phylogenetic analysis, quantitative RT-PCR enzyme expression analysis
gene CYP82E4v1, DNA and amino acid sequence determination and analysis, real-time PCR enzyme expression analysis
Q38Q86
gene CYP82E5, DNA and amino acid sequence determination and analysis, phylogenetic analysis, quantitative RT-PCR enzyme expression analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
-
while the nornicotine content of most commercial burley tobacco is low, a process termed conversion can bestow considerably increased nornicotine levels in a portion of the plants within the population. Transcript accumulation of isoform CYP82E4 is enhanced as much as 80fold in converter vs nonconverter tobacco. An optimized RNAi construct 82E4Ri298 suppresses nicotine to nornicotine conversion from 98% to as low as 0.8% in a strong converter tobacco line, a rate of nornicotine production that is about 3.6fold lower than typically detected in commercial varieties. Greenhouse-grown transgenic plants transformed with the RNAi construct are morphologically indistinguishable from the empty vector or wild-type controls
nutrition
nutrition
-
inhibition of gene expression by RNAi leads to up ot sixfold decrease in nornicotine content with concomitant decrease in N'-nitrosonornicotine and total tobacco-specific nitrosamines
nutrition
-
while the nornicotine content of most commercial burley tobacco is low, a process termed conversion can bestow considerably increased nornicotine levels in a portion of the plants within the population. Transcript accumulation of isoform CYP82E4 is enhanced as much as 80fold in converter vs nonconverter tobacco. An optimized RNAi construct 82E4Ri298 suppresses nicotine to nornicotine conversion from 98% to as low as 0.8% in a strong converter tobacco line, a rate of nornicotine production that is about 3.6fold lower than typically detected in commercial varieties. Greenhouse-grown transgenic plants transformed with the RNAi construct are morphologically indistinguishable from the empty vector or wild-type controls
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Siminszky, B.; Gavilano, L.; Bowen, S.W.; Dewey, R.E.
Conversion of nicotine to nornicotine in Nicotiana tabacum is mediated by CYP82E4, a cytochrome P450 monooxygenase
Proc. Natl. Acad. Sci. USA
102
14919-14924
2005
Nicotiana tabacum (Q38Q86), Nicotiana tabacum
brenda
Yamanaka, H.; Nakajima, M.; Fukami, T.; Sakai, H.; Nakamura, A.; Katoh, M.; Takamiya, M.; Aoki, Y.; Yokoi, T.
CYP2A6 AND CYP2B6 are involved in nornicotine formation from nicotine in humans: interindividual differences in these contributions
Drug Metab. Dispos.
33
1811-1818
2005
Homo sapiens
brenda
Gavilano, L.B.; Coleman, N.P.; Burnley, L.E.; Bowman, M.L.; Kalengamaliro, N.E.; Hayes, A.; Bush, L.; Siminszky, B.
Genetic engineering of Nicotiana tabacum for reduced nornicotine content
J. Agric. Food Chem.
54
9071-9078
2006
Nicotiana tabacum
brenda
Gavilano, L.B.; Coleman, N.P.; Bowen, S.W.; Siminszky, B.
Functional analysis of nicotine demethylase genes reveals insights into the evolution of modern tobacco
J. Biol. Chem.
282
249-256
2007
Nicotiana tabacum, Nicotiana tomentosiformis (A1YJE2), Nicotiana tomentosiformis (A1YJE3), Nicotiana tomentosiformis
brenda
Hao, D.; Yeoman, M.M.
Evidence in favor of an oxidative N-demethylation of nicotine to nornicotine in tobacco cell cultures
J. Plant Physiol.
152
420-426
1998
Nicotiana tabacum
-
brenda
Chakrabarti, M.; Meekins, K.M.; Gavilano, L.B.; Siminszky, B.
Inactivation of the cytochrome P450 gene CYP82E2 by degenerative mutations was a key event in the evolution of the alkaloid profile of modern tobacco
New Phytol.
175
565-574
2007
Nicotiana sylvestris (A7KMF3), Nicotiana sylvestris
brenda
Lewis, R.S.; Jack, A.M.; Morris, J.W.; Robert, V.J.; Gavilano, L.B.; Siminszky, B.; Bush, L.P.; Hayes, A.J.; Dewey, R.E.
RNA interference (RNAi)-induced suppression of nicotine demethylase activity reduces levels of a key carcinogen in cured tobacco leaves
Plant Biotechnol. J.
6
346-354
2008
Nicotiana tabacum
brenda
Gavilano, L.B.; Siminszky, B.
Isolation and characterization of the cytochrome P450 gene CYP82E5v2 that mediates nicotine to nornicotine conversion in the green leaves of tobacco
Plant Cell Physiol.
48
1567-1574
2007
Nicotiana tabacum (A9QNE6), Nicotiana tabacum
brenda
Xu, D.; Shen, Y.; Chappell, J.; Cui, M.; Nielsen, M.T.
Biochemical and molecular characterization of nicotine demethylase in tobacco
Physiol. Plant.
129
307-319
2007
Nicotiana tabacum (Q38Q87)
-
brenda
Lian, J.; Wang, D.; Xie, J.
Data mining of nicotine demethylase genes in modern tobacoo
Adv. Mater. Res.
787
356-360
2013
Nicotiana tabacum
-
brenda
Cai, B.; Bush, L.
Variable nornicotine enantiomeric composition caused by nicotine demethylase CYP82E4 in tobacco leaf
J. Agric. Food Chem.
60
11586-11591
2012
Nicotiana tabacum
brenda
Cai, B.; Siminszky, B.; Chappell, J.; Dewey, R.; Bush, L.
Enantioselective demethylation of nicotine as a mechanism for variable nornicotine composition in tobacco leaf
J. Biol. Chem.
287
42804-42811
2012
Nicotiana tabacum
brenda
Pakdeechanuan, P.; Teoh, S.; Shoji, T.; Hashimoto, T.
Non-functionalization of two CYP82E nicotine N-demethylase genes abolishes nornicotine formation in nicotiana langsdorffii
Plant Cell Physiol.
53
2038-2046
2012
Nicotiana alata (J7MDR0), Nicotiana alata (J7M5N9), Nicotiana alata (J7MB22), Nicotiana alata (J7M2E3), Nicotiana alata, Nicotiana langsdorffii (J7M8Q0), Nicotiana langsdorffii
brenda
Wang, S.; Yang, S.; An, B.; Wang, S.; Yin, Y.; Lu, Y.; Xu, Y.; Hao, D.
Molecular dynamics analysis reveals structural insights into mechanism of nicotine N-demethylation catalyzed by tobacco cytochrome P450 mono-oxygenase
PLoS ONE
6
e23342
2011
Nicotiana tabacum
brenda
Liedschulte, V.; Schwaar, J.D.; Laparra, H.; Vuarnoz, A.; Philippon, B.; Bakaher, N.; Sierro, N.; Bovet, L.; Lang, G.; Goepfert, S.
Identification of CYP82E21 as a functional nicotine N-demethylase in tobacco flowers
Phytochemistry
131
9-16
2016
Nicotiana tabacum
brenda
Zhao, D.; Qin, L.J.; Zhao, D.G.
RNA interference of the nicotine demethylase gene CYP82E4v1 reduces nornicotine content and enhances Myzus persicae resistance in Nicotiana tabacum L
Plant Physiol. Biochem.
107
214-221
2016
Nicotiana tabacum (Q38Q86), Nicotiana tabacum
brenda
Song, Z.; Sui, X.; Li, M.; Gao, Y.; Li, W.; Zhao, L.; Li, F.; Yao, X.; Liu, C.; Wang, B.
Development of a nornicotine-reduced flue-cured tobacco line via EMS mutagenesis of nicotine N-demethylase genes
Plant Signal. Behav.
15
1710053
2020
Nicotiana tabacum (Q38Q87), Nicotiana tabacum (A1XEH1), Nicotiana tabacum (E5G962)
brenda
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