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Information on EC 1.14.13.128 - 7-methylxanthine demethylase
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1.14.13.128 7-methylxanthine demethylaseIUBMB Comments
A non-heme iron oxygenase. The enzyme from the bacterium Pseudomonas putida prefers NADH over NADPH. The enzyme is specific for 7-methylxanthine . Forms part of the caffeine degradation pathway.
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Word Map
- 1.14.13.128
- putida
-
demethylation
- theophylline
-
bioreactors
-
uric
- coffee
-
trimethyl
-
costly
- 1,3,7-trimethylxanthine
- rhodococcus
- paraxanthine
- 3,7-dimethylxanthine
- formaldehyde
- aminopyrine
- alcaligenes
-
rieske
-
broad-specificity
-
non-heme
- 3-methylxanthine
-
oxygen-dependent
- methylxanthines
-
commences
-
bioprocess
- klebsiella
- pharmacology
- medicine
The enzyme appears in viruses and cellular organisms
Synonyms
caffeine demethylase, bacterial n-demethylase, theobromine demethylase, methylxanthine n-demethylase, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
7-methylxanthine-specific N-demethylase
bacterial N-demethylase
methylxanthine N-demethylase
ndmA
NdmC
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
7-methylxanthine + O2 + NAD(P)H + H+ = xanthine + NAD(P)+ + H2O + formaldehyde
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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SYSTEMATIC NAME
IUBMB Comments
7-methylxanthine:oxygen oxidoreductase (demethylating)
A non-heme iron oxygenase. The enzyme from the bacterium Pseudomonas putida prefers NADH over NADPH. The enzyme is specific for 7-methylxanthine [2]. Forms part of the caffeine degradation pathway.
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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
1,3,7-trimethylxanthine + O2 + NAD(P)H + H+
3,7-dimethylxanthine + formaldehyde + NAD(P)+
-
i.e. caffeine
i.e. theobromine
-
?
1,3,7-trimethylxanthine + O2 + NADPH + H+
1,3-dimethylxanthine + formaldehyde + NADP+ + H2O
-
i.e. caffeine
i.e. theophylline
-
?
1,3,7-trimethylxanthine + O2 + NADPH + H+
1,7-dimethylxanthine + formaldehyde + NADP+ + H2O
-
i.e. caffeine
i.e. paraxanthine
-
?
1,7-dimethylxanthine + O2 + NADPH + H+
7-methylxanthine + NADP+ + H2O + formaldehyde
-
i.e. paraxanthine, activity of the reductase component of the N-demethylase holoenzyme (Ccr) with NADPH is 22% of that with NADH. The enzyme also catalyzes the further demethylation of the product 7-methylxanthine to xanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
3,7-dimethylxanthine + O2 + NAD(P)H + H+
monomethylxanthine + formaldehyde + NADP+
-
theobromine demethylase
-
-
?
3-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
-
3-methylxanthine demethylation is 12% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
7-methylxanthine + O2 + NAD(P)H + H+
xanthine + formaldehyde + NADP+
-
heteroxanthine demethylase, substrate-selective
-
-
?
7-methylxanthine + O2 + NADPH + H+
xanthine + NADP+ + H2O + formaldehyde
-
-
-
-
?
caffeine + 2 O2 + 2 NADH + 2 H+
7-methylxanthine + 2 NAD+ + 2 H2O + 2 formaldehyde
-
i.e. 1,3,7-trimethylxanthine. Caffeine demethylation is 7% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
caffeine + 3 O2 + 3 NADH + 3 H+
xanthine + 3 NAD+ + 3 H2O + 3 formaldehyde
-
i.e. 1,3,7-trimethylxanthine. Caffeine demethylation is 7% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
caffeine + O2 + NADH + H+
1,7-dimethylxanthine + NAD+ + H2O + formaldehyde
-
i.e. 1,3,7-trimethylxanthine. Caffeine demethylation is 7% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
theobromine + 2 O2 + 2 NADH + 2 H+
xanthine + 2 NAD+ + 2 H2O + 2 formaldehyde
-
i.e. 3,7-dimethylxanthine. Theobromine demethylation is 13% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
theobromine + O2 + NADH + H+
3-methylxanthine + NAD+ + H2O + formaldehyde
-
i.e. 3,7-dimethylxanthine. Theobromine demethylation is 13% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
theobromine + O2 + NADH + H+
7-methylxanthine + NAD+ + H2O + formaldehyde
-
i.e. 3,7-dimethylxanthine. Theobromine demethylation is 13% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
theophylline + 2 O2 + 2 NADH + 2 H+
xanthine + 2 NAD+ + 2 H2O + 2 formaldehyde
-
1,3-dimethylxanthine. Theophylline demethylation is 3% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
theophylline + O2 + NADH + H+
1-methylxanthine + NAD+ + H2O + formaldehyde
-
1,3-dimethylxanthine. Theophylline demethylation is 3% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
1,7-dimethylxanthine + 2 O2 + 2 NADH + 2 H+
xanthine + 2 NAD+ + 2 H2O + 2 formaldehyde
-
i.e. paraxanthine, NADH is the preferred cofactor of reductase component of the N-demethylase holoenzyme (Ccr). The product 7-methylxanthine is further demethylated to xanthine. 1,7-Dimethylxanthine (paraxanthine) demethylation is 22% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
1,7-dimethylxanthine + 2 O2 + 2 NADH + 2 H+
xanthine + 2 NAD+ + 2 H2O + 2 formaldehyde
-
i.e. paraxanthine, NADH is the preferred cofactor of reductase component of the N-demethylase holoenzyme (Ccr). The product 7-methylxanthine is further demethylated to xanthine. 1,7-Dimethylxanthine (paraxanthine) demethylation is 22% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
1,7-dimethylxanthine + 2 O2 + 2 NADPH + 2 H+
xanthine + 2 NADP+ + 2 H2O + 2 formaldehyde
-
i.e. paraxanthine, activity of the reductase component of the N-demethylase holoenzyme (Ccr) with NADPH is 22% of that with NADH. The enzyme also catalyzes the further demethylation of the product 7-methylxanthine to xanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
1,7-dimethylxanthine + 2 O2 + 2 NADPH + 2 H+
xanthine + 2 NADP+ + 2 H2O + 2 formaldehyde
-
i.e. paraxanthine, activity of the reductase component of the N-demethylase holoenzyme (Ccr) with NADPH is 22% of that with NADH. The enzyme also catalyzes the further demethylation of the product 7-methylxanthine to xanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
1,7-dimethylxanthine + O2 + NADH + H+
7-methylxanthine + NAD+ + H2O + formaldehyde
-
i.e. paraxanthine, NADH is the preferred cofactor of reductase component of the N-demethylase holoenzyme (Ccr). The product 7-methylxanthine is further demethylated to xanthine. 1,7-Dimethylxanthine (paraxanthine) demethylation is 22% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
1,7-dimethylxanthine + O2 + NADH + H+
7-methylxanthine + NAD+ + H2O + formaldehyde
-
i.e. paraxanthine, NADH is the preferred cofactor of reductase component of the N-demethylase holoenzyme (Ccr). The product 7-methylxanthine is further demethylated to xanthine. 1,7-Dimethylxanthine (paraxanthine) demethylation is 22% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
7-methylxanthine + O2 + NAD(P)H + H+
xanthine + NAD(P)+ + H2O + formaldehyde
-
part of the caffeine degradation pathway in Pseudomonas putida
-
-
?
7-methylxanthine + O2 + NAD(P)H + H+
xanthine + NAD(P)+ + H2O + formaldehyde
-
part of the caffeine degradation pathway in Pseudomonas putida
-
-
?
7-methylxanthine + O2 + NAD(P)H + H+
xanthine + NAD(P)+ + H2O + formaldehyde
-
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
-
-
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
-
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
specific substrate
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
-
the enzyme most actively demethylates 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
the N7-demethylation reaction absolutely requires a unique, tightly bound protein complex composed of NdmC, NdmD, and NdmE. NdmE functions as a noncatalytic subunit that serves a structural role in the complexation of the oxygenase (NdmC) and Rieske domains (NdmD)
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
immediate degradation via the NdmCDE complex
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
NdmC specifically detaches methyl groups from the N-7 position of methylxanthine derivatives
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
-
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
specific substrate
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
the N7-demethylation reaction absolutely requires a unique, tightly bound protein complex composed of NdmC, NdmD, and NdmE. NdmE functions as a noncatalytic subunit that serves a structural role in the complexation of the oxygenase (NdmC) and Rieske domains (NdmD)
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
immediate degradation via the NdmCDE complex
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
NdmC specifically detaches methyl groups from the N-7 position of methylxanthine derivatives
-
-
?
caffeine + O2 + NADH + H+
theobromine + NAD+ + H2O + formaldehyde
-
-
-
?
caffeine + O2 + NADH + H+
theobromine + NAD+ + H2O + formaldehyde
-
i.e. 1,3,7-trimethylxanthine. Caffeine demethylation is 7% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
caffeine + O2 + NADH + H+
theobromine + NAD+ + H2O + formaldehyde
-
-
-
?
theophylline + O2 + NADH + H+
3-methylxanthine + NAD+ + H2O + formaldehyde
-
-
-
?
theophylline + O2 + NADH + H+
3-methylxanthine + NAD+ + H2O + formaldehyde
-
1,3-dimethylxanthine. Theophylline demethylation is 3% of the activity compared to demethylation of 7-methylxanthine. Activity is absolutely dependent of oxygen as a cosubstrate
-
-
?
theophylline + O2 + NADH + H+
3-methylxanthine + NAD+ + H2O + formaldehyde
-
-
-
?
additional information
?
-
-
Ndm exhibits broad-based activity towards caffeine, theophylline, theobromine, 7-methylxanthine and 3-methylxanthine, all of which are growth substrates for Pseudomonas putida CBB5. Production of xanthine from all of these methylxanthines is confirmed. Ndm is most active on 7-methylxanthine, followed by 1,7-dimethylxanthine (paraxanthine), theobromine, 3-methylxanthine, caffeine and theophylline. Ndm does not catalyse O-demethylation of vanillate or vanillin, even after prolonged incubation
-
-
?
additional information
?
-
-
the metabolite is 1,3-dimethylxanthine, i.e. theophylline, is produced by the demethylation in the 7th position of the purine ring, mainly in fungi, overview
-
-
?
additional information
?
-
-
no activity of the heteroxanthine demethylase, when either caffeine or dimethylxanthines are used as substrates
-
-
?
additional information
?
-
caffeine, paraxanthine, and theobromine are not demethylated by the enzyme
-
-
?
additional information
?
-
no activity toward caffeine or theobromine
-
-
?
additional information
?
-
enzyme NdmA catalyzes NADH-dependent N1-demethylation of caffeine to theobromine and theophylline to 3-methylxanthine, and subsequently to 7-methylxanthine, and xanthine. Theobromine is the major product due to highly selective N1-demethylation caffeine by NdmA. But the minor production of paraxanthine from caffeine is due to slight promiscuity of the NdmA towards the N3-position on the caffeine molecule. Direct N-demethylation of caffeine at the N3 position does not occur appreciably with the three N-demethylases involved in caffeine degradation in CBB5
-
-
?
additional information
?
-
-
Ndm exhibits broad-based activity towards caffeine, theophylline, theobromine, 7-methylxanthine and 3-methylxanthine, all of which are growth substrates for Pseudomonas putida CBB5. Production of xanthine from all of these methylxanthines is confirmed. Ndm is most active on 7-methylxanthine, followed by 1,7-dimethylxanthine (paraxanthine), theobromine, 3-methylxanthine, caffeine and theophylline. Ndm does not catalyse O-demethylation of vanillate or vanillin, even after prolonged incubation
-
-
?
additional information
?
-
enzyme NdmA catalyzes NADH-dependent N1-demethylation of caffeine to theobromine and theophylline to 3-methylxanthine, and subsequently to 7-methylxanthine, and xanthine. Theobromine is the major product due to highly selective N1-demethylation caffeine by NdmA. But the minor production of paraxanthine from caffeine is due to slight promiscuity of the NdmA towards the N3-position on the caffeine molecule. Direct N-demethylation of caffeine at the N3 position does not occur appreciably with the three N-demethylases involved in caffeine degradation in CBB5
-
-
?
additional information
?
-
caffeine, paraxanthine, and theobromine are not demethylated by the enzyme
-
-
?
additional information
?
-
-
caffeine, paraxanthine, and theobromine are not demethylated by the enzyme
-
-
?
additional information
?
-
no activity toward caffeine or theobromine
-
-
?
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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
1,3,7-trimethylxanthine + O2 + NAD(P)H + H+
3,7-dimethylxanthine + formaldehyde + NAD(P)+
-
i.e. caffeine
i.e. theobromine
-
?
1,3,7-trimethylxanthine + O2 + NADPH + H+
1,3-dimethylxanthine + formaldehyde + NADP+ + H2O
-
i.e. caffeine
i.e. theophylline
-
?
1,3,7-trimethylxanthine + O2 + NADPH + H+
1,7-dimethylxanthine + formaldehyde + NADP+ + H2O
-
i.e. caffeine
i.e. paraxanthine
-
?
7-methylxanthine + O2 + NAD(P)H + H+
xanthine + NAD(P)+ + H2O + formaldehyde
-
part of the caffeine degradation pathway in Pseudomonas putida
-
-
?
7-methylxanthine + O2 + NAD(P)H + H+
xanthine + NAD(P)+ + H2O + formaldehyde
-
part of the caffeine degradation pathway in Pseudomonas putida
-
-
?
7-methylxanthine + O2 + NAD(P)H + H+
xanthine + NAD(P)+ + H2O + formaldehyde
-
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
-
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
specific substrate
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
the N7-demethylation reaction absolutely requires a unique, tightly bound protein complex composed of NdmC, NdmD, and NdmE. NdmE functions as a noncatalytic subunit that serves a structural role in the complexation of the oxygenase (NdmC) and Rieske domains (NdmD)
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
immediate degradation via the NdmCDE complex
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
-
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
specific substrate
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
the N7-demethylation reaction absolutely requires a unique, tightly bound protein complex composed of NdmC, NdmD, and NdmE. NdmE functions as a noncatalytic subunit that serves a structural role in the complexation of the oxygenase (NdmC) and Rieske domains (NdmD)
-
-
?
7-methylxanthine + O2 + NADH + H+
xanthine + NAD+ + H2O + formaldehyde
immediate degradation via the NdmCDE complex
-
-
?
caffeine + O2 + NADH + H+
theobromine + NAD+ + H2O + formaldehyde
-
-
-
?
caffeine + O2 + NADH + H+
theobromine + NAD+ + H2O + formaldehyde
-
-
-
?
additional information
?
-
-
the metabolite is 1,3-dimethylxanthine, i.e. theophylline, is produced by the demethylation in the 7th position of the purine ring, mainly in fungi, overview
-
-
?
additional information
?
-
caffeine, paraxanthine, and theobromine are not demethylated by the enzyme
-
-
?
additional information
?
-
no activity toward caffeine or theobromine
-
-
?
additional information
?
-
enzyme NdmA catalyzes NADH-dependent N1-demethylation of caffeine to theobromine and theophylline to 3-methylxanthine, and subsequently to 7-methylxanthine, and xanthine. Theobromine is the major product due to highly selective N1-demethylation caffeine by NdmA. But the minor production of paraxanthine from caffeine is due to slight promiscuity of the NdmA towards the N3-position on the caffeine molecule. Direct N-demethylation of caffeine at the N3 position does not occur appreciably with the three N-demethylases involved in caffeine degradation in CBB5
-
-
?
additional information
?
-
enzyme NdmA catalyzes NADH-dependent N1-demethylation of caffeine to theobromine and theophylline to 3-methylxanthine, and subsequently to 7-methylxanthine, and xanthine. Theobromine is the major product due to highly selective N1-demethylation caffeine by NdmA. But the minor production of paraxanthine from caffeine is due to slight promiscuity of the NdmA towards the N3-position on the caffeine molecule. Direct N-demethylation of caffeine at the N3 position does not occur appreciably with the three N-demethylases involved in caffeine degradation in CBB5
-
-
?
additional information
?
-
caffeine, paraxanthine, and theobromine are not demethylated by the enzyme
-
-
?
additional information
?
-
-
caffeine, paraxanthine, and theobromine are not demethylated by the enzyme
-
-
?
additional information
?
-
no activity toward caffeine or theobromine
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
-
activity of Ccr (reductase component of the N-demethylase holoenzyme) with NADPH is 22% of that with NADH
[2Fe-2S]-center
NdmA enzyme is a Rieske (2Fe-2S) non-heme iron monooxygenase that requires a partner reductase, NdmD, to transfer electrons from NADH
NADH
-
preferred cofactor of Ccr (reductase component of the N-demethylase holoenzyme)
NADH
NdmA enzyme is a Rieske (2Fe-2S) non-heme iron monooxygenase that requires a partner reductase, NdmD, to transfer electrons from NADH
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Iron
Fe2+
-
preincubation of Ndm for 15 min with 1 mM Fe2+, followed by desalting, increases the iron content to 20.1 mol per mol hexameric N-demethylase component (Ndm) of the N-demethylase holoenzyme. After this treatment, Ndm specific activity increases about 6fold (when 50 mM Fe2+ is present in the enzyme reaction mixture). N-Demethylase component (Ndm) of the N-demethylase holoenzyme is deduced to be a Rieske [2Fe-2S]-domain containing non-haem iron oxygenase
Iron
a Rieske nonheme iron monooxygenase. The enzyme contains 2 mol of iron per mol of monomer
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Zn2+
-
theobromine demethylase enzyme is inhibited by Zn2+, which generates the accumulation of theobromine
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0504
1,7-dimethylxanthine
-
pH 7.5, 30°C, kinetic parameters for two-subunit N-demethylase component (Ndm), in the presence of saturating amounts of Ccr (reductase component with cytochrome c reductase activity) and 50 mM Fe2+
1.1
3,7-Dimethylxanthine
-
theobromine demethylase, pH and temperature not specified in the publication
0.0153
7-methylxanthine
in 50 mM potassium phosphate buffer (pH 7.5) at 30°C
0.0638
7-methylxanthine
-
pH 7.5, 30°C, kinetic parameters for two-subunit N-demethylase component (Ndm), in the presence of saturating amounts of Ccr (reductase component with cytochrome c reductase activity) and 50 mM Fe2+
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.27
1,7-dimethylxanthine
-
pH 7.5, 30°C, kinetic parameters for two-subunit N-demethylase component (Ndm), in the presence of saturating amounts of Ccr (reductase component with cytochrome c reductase activity) and 50 mM Fe2+
0.16
7-methylxanthine
in 50 mM potassium phosphate buffer (pH 7.5) at 30°C
1.58
7-methylxanthine
-
pH 7.5, 30°C, kinetic parameters for two-subunit N-demethylase component (Ndm), in the presence of saturating amounts of Ccr (reductase component with cytochrome c reductase activity) and 50 mM Fe2+
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5.4
1,7-dimethylxanthine
-
pH 7.5, 30°C, kinetic parameters for two-subunit N-demethylase component (Ndm), in the presence of saturating amounts of Ccr (reductase component with cytochrome c reductase activity) and 50 mM Fe2+
10.17
7-methylxanthine
in 50 mM potassium phosphate buffer (pH 7.5) at 30°C
24.8
7-methylxanthine
-
pH 7.5, 30°C, kinetic parameters for two-subunit N-demethylase component (Ndm), in the presence of saturating amounts of Ccr (reductase component with cytochrome c reductase activity) and 50 mM Fe2+
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.3
7.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
30 - 35
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isolated from coffee plantation soil in Ooty, India
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
soil bacterium Pseudomonas putida strain CBB5 can use caffeine (1,3,7-trimethylxanthine) as a sole carbon and nitrogen source
brenda
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soil bacterium Pseudomonas putida strain CBB5 can use caffeine (1,3,7-trimethylxanthine) as a sole carbon and nitrogen source
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brenda
strain NCIM 5235 can utilize caffeine as sole source of carbon and nitrogen for growth
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
physiological function
additional information
based on the sequence of a genomic fragment, caffeine demethylation enzyme system found in Pseudomonas sp. is predicted to consist of a two-component Rieske monooxygenases namely NdmA and NdmB specific towards methyl groups at 1 and 3 positions in xanthine ring respectively and one kind of three-component Rieske monooxygenase system comprising a monooxygenase NdmC specific towards 7-methylxanthine, a reductase component NdmD and a structural protein NdmE. NdmD also acts as the reductase component for NdmA and NdmB. The Rieske domain present in NdmD serves to function as an electron transfer domain during catalysis by NdmC as it lacks its own Rieske domain. NdmC forms a large multi-subunit complex comprising 2 monomeric units of each NdmC, NdmD, and NdmE and follows the typical electron flow pattern of Rieske oxygenases. The N-terminal Rieske domain found in NdmD is a product of domain shuffling between NdmC and NdmD during evolution and is not required for its reductase activity
evolution
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catabolism of caffeine in microorganisms commences via two possible mechanisms: demethylation and oxidation. Through the demethylation route, the major metabolite formed in fungi is theophylline, whereas theobromine is the major metabolite in bacteria
evolution
the N-terminal Rieske domain found in NdmD is a product of domain shuffling between NdmC and NdmD during evolution and is not required for its reductase activity
metabolism
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catabolism of caffeine in microorganisms commences via two possible mechanisms: demethylation and oxidation. Through the demethylation route, the major metabolite formed in fungi is theophylline, whereas theobromine is the major metabolite in bacteria. Catabolism of caffeine in microorganisms, overview
metabolism
Rieske nonheme iron oxygenases (ROs) catalyze the initial oxygenation reaction of aromatic compounds by enantio- and regiospecific reactions. The type of RO in Pseudomonas putida strain CBB5, consists of NdmA, NdmB, and NdmC, which specifically detach methyl groups from the N-1, N-3, and N-7 positions of methylxanthine derivatives, respectively. A single formaldehyde is produced whenever one N-linked methyl group is detached, indicating that NdmA, NdmB, and NdmC are monooxygenases.The N-demethylation of caffeine to xanthine occurs via three steps; NdmA and NdmB catalyze the initial two steps of N-demethylation, and the intermediate product, 7-methylxanthine, is further catalyzed to xanthine by an unusual RO-reductase complex, the NdmCDE heterotrimer. Heterohexamerization of NdmA and NdmB under physiological conditions. NdmD is the RO reductase that forms a stable ternary complex with NdmC and NdmE (NdmCDE). Since NdmC detaches the N-7 methyl group from methylxanthine derivatives, the NdmCDE complex is responsible for the last N-demethylation step of caffeine to xanthine. But NdmD is also needed by both NdmA and NdmB for electron transport from NADH to the oxygen activation site. Therefore, it is expected that transient interaction would exist between them. Electron transfer pathway from the ferredoxin domain of NdmD to caffeine in the catalytic site of NdmA. Enzyme complex structure analysis structure-function analysis, overview
metabolism
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Rieske nonheme iron oxygenases (ROs) catalyze the initial oxygenation reaction of aromatic compounds by enantio- and regiospecific reactions. The type of RO in Pseudomonas putida strain CBB5, consists of NdmA, NdmB, and NdmC, which specifically detach methyl groups from the N-1, N-3, and N-7 positions of methylxanthine derivatives, respectively. A single formaldehyde is produced whenever one N-linked methyl group is detached, indicating that NdmA, NdmB, and NdmC are monooxygenases.The N-demethylation of caffeine to xanthine occurs via three steps; NdmA and NdmB catalyze the initial two steps of N-demethylation, and the intermediate product, 7-methylxanthine, is further catalyzed to xanthine by an unusual RO-reductase complex, the NdmCDE heterotrimer. Heterohexamerization of NdmA and NdmB under physiological conditions. NdmD is the RO reductase that forms a stable ternary complex with NdmC and NdmE (NdmCDE). Since NdmC detaches the N-7 methyl group from methylxanthine derivatives, the NdmCDE complex is responsible for the last N-demethylation step of caffeine to xanthine. But NdmD is also needed by both NdmA and NdmB for electron transport from NADH to the oxygen activation site. Therefore, it is expected that transient interaction would exist between them. Electron transfer pathway from the ferredoxin domain of NdmD to caffeine in the catalytic site of NdmA. Enzyme complex structure analysis structure-function analysis, overview
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physiological function
the enzyme NdmA catalyzes NADH-dependent N1-demethylation of caffeine to theobromine and theophylline to 3-methylxanthine, and subsequently to 7-methylxanthine, and xanthine. The oxidoreductase NdmD, UniProt ID H9N291, catalyzes the oxidation of NADH and transfers electrons to NdmA and NdmB, which catalyze the N-demethylation reaction
physiological function
Pseudomonas sp. NCIM 5235 is a caffeine-degrading bacterial strain that metabolizes caffeine by sequential demethylation using methylxanthine demethylases, including 7-methylxanthine demethylase NdmC. These enzymes belong to the class of two-component Rieske oxygenases and require an oxidoreductase, NdmD, for efficient catalysis. Three oxygenases (NdmA, NdmB, and NdmC) specific towards methyl groups at 1, 3, and 7 positions in xanthine ring share a common reductase component, NdmD, analysis of NdmD parameters and function, overview. Another structural protein and oxidoreductase NdmE has also been shown to be required for catalysis by NdmC. Rieske oxygenases are an important class of enzymes that have been reported to play a major role in the degradation of xenobiotic compounds and drugs
physiological function
some bacteria, such as Pseudomonas putida strain CBB5, utilize caffeine as a sole carbon and nitrogen source by degrading it through sequential N-demethylation catalyzed by five enzymes: NdmA, NdmB, NdmC, NdmD, and NdmE. Enzyme NdmC specifically detaches methyl groups from the N-7 position of methylxanthine derivatives, NdmC is a monooxygenase
physiological function
-
the enzyme NdmA catalyzes NADH-dependent N1-demethylation of caffeine to theobromine and theophylline to 3-methylxanthine, and subsequently to 7-methylxanthine, and xanthine. The oxidoreductase NdmD, UniProt ID H9N291, catalyzes the oxidation of NADH and transfers electrons to NdmA and NdmB, which catalyze the N-demethylation reaction
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physiological function
-
some bacteria, such as Pseudomonas putida strain CBB5, utilize caffeine as a sole carbon and nitrogen source by degrading it through sequential N-demethylation catalyzed by five enzymes: NdmA, NdmB, NdmC, NdmD, and NdmE. Enzyme NdmC specifically detaches methyl groups from the N-7 position of methylxanthine derivatives, NdmC is a monooxygenase
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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). A0A6J5FNJ9_9BURK
283
0
32432
TrEMBL
-
A0A2Z2NZB2_9GAMM
288
0
32118
TrEMBL
-
A0A644VYY0_9ZZZZ
287
0
32091
TrEMBL
other Location (Reliability: 1)
A0A644VZH6_9ZZZZ
283
0
31853
TrEMBL
other Location (Reliability: 5)
A0A6J5H290_9BURK
292
0
32355
TrEMBL
-