Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(R)-nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2
(R)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
isoforms CYP82E4, CYP82E5v2, and CYP82E10 demethylate (R)-nicotine 3, 10, and 10fold faster than (S)-nicotine, respectively
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
nicotine + NADPH + H+
nornicotine + NADP+
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
additional information
?
-
-
isoforms CYP2A6 and CYP2B6 significantly contribute to the nicotine N-demethylation at low and high substrate concentrations, respectively
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
CYP82E4 selectively demethylates (S)-nicotine
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
only isoform CYP82E4 can significantly convert (S)-nicotine to (S)-nornicotine
-
-
?
nicotine + NADPH + H+
nornicotine + NADP+
-
-
-
-
?
nicotine + NADPH + H+
nornicotine + NADP+
Q38Q86
-
-
-
?
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
-
-
-
?
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
demethylates nicotine to form nornicotine, a precursor to the nitrosamine N'-nitrosonornicotine
-
-
?
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
six putative substrate recognition sites
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
-
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
-
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
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
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(R)-nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2
(R)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
isoforms CYP82E4, CYP82E5v2, and CYP82E10 demethylate (R)-nicotine 3, 10, and 10fold faster than (S)-nicotine, respectively
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
nicotine + NADPH + H+
nornicotine + NADP+
nicotine + NADPH + O2 + H+
nornicotine + formaldehyde + NADP+ + H2O
demethylates nicotine to form nornicotine, a precursor to the nitrosamine N'-nitrosonornicotine
-
-
?
nicotine + O2 + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
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
-
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
CYP82E4 selectively demethylates (S)-nicotine
-
-
?
(S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2
(S)-nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
-
only isoform CYP82E4 can significantly convert (S)-nicotine to (S)-nornicotine
-
-
?
nicotine + NADPH + H+
nornicotine + NADP+
-
-
-
-
?
nicotine + NADPH + H+
nornicotine + NADP+
Q38Q86
-
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
-
-
-
?
nicotine + [reduced NADPH-hemoprotein reductase] + O2
nornicotine + formaldehyde + [oxidized NADPH-hemoprotein reductase] + H2O
Q38Q86
-
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
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
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
E375K
loss of catalytic activity
W422L
loss of catalytic activity
K269N
isoform CYP82E3 variant, no catalytic activity
K269N/I274Null
isoform CYP82E3 variant, no catalytic activity
K269N/I274Null/T279A
isoform CYP82E3 variant, no catalytic activity
C330W
-
inactive
C330W
isoform CYP82E3 variant, active
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
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
-
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
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
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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 characterizations 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 (J7M2E3), Nicotiana alata (J7M5N9), Nicotiana alata (J7MB22), Nicotiana alata (J7MDR0), 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