Information on EC 1.5.1.33 - pteridine reductase

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The expected taxonomic range for this enzyme is: Trypanosomatidae

EC NUMBER
COMMENTARY hide
1.5.1.33
-
RECOMMENDED NAME
GeneOntology No.
pteridine reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH + 2 H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
5,6,7,8-tetrahydrobiopterin:NADP+ oxidoreductase
The enzyme from Leishmania (both amastigote and promastigote forms) catalyses the reduction by NADPH of folate and a wide variety of unconjugated pterins, including biopterin, to their tetrahydro forms. It also catalyses the reduction of 7,8-dihydropterins and 7,8-dihydrofolate to their tetrahydro forms. In contrast to EC 1.5.1.3 (dihydrofolate reductase) and EC 1.5.1.34 (6,7-dihydropteridine reductase), pteridine reductase will not catalyse the reduction of the quinonoid form of dihydrobiopterin. The enzyme is specific for NADPH; no activity has been detected with NADH. It also differs from EC 1.5.1.3 (dihydrofolate reductase) in being specific for the Si-face of NADPH.
CAS REGISTRY NUMBER
COMMENTARY hide
131384-61-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
Y strain
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 biopterin + 3 NADPH + 3 H+
dihydrobiopterin + tetrahydrobiopterin + 3 NADP+
show the reaction diagram
6-biopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
biopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
biopterin + NADPH + H+
dihydrobiopterin + NADP+
show the reaction diagram
dihydrobiopterin + NADPH
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
Dihydrobiopterin + NADPH
?
show the reaction diagram
dihydrobiopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
Dihydrofolate + NADPH
5,6,7,8-Tetrahydrofolate + NADP+
show the reaction diagram
Dihydroneopterin + NADPH
?
show the reaction diagram
dihydrosepiapterin + NADPH
?
show the reaction diagram
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
folate + NADPH + H+
7,8-dihydrofolate and tetrahydrofolate + NADP+
show the reaction diagram
quinonoid 6,7-dimethyl-7,8-dihydropterin + NADPH + H+
?
show the reaction diagram
quinonoid dihydrobiopterin + NADPH + H+
tetrahydrobiopterin + NADP+
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 biopterin + 3 NADPH + 3 H+
dihydrobiopterin + tetrahydrobiopterin + 3 NADP+
show the reaction diagram
6-biopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
biopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
folate + NADPH + H+
7,8-dihydrofolate and tetrahydrofolate + NADP+
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2-amino-2,3-dihydro-1H-benzimidazol-1-yl)(phenyl)methanone
-
-
(2E,4E)-N-(2-methylpropyl)dodeca-2,4-dienamide
-
-
(2E,4E)-N-(2-methylpropyl)octadeca-2,4-dienamide
-
-
(2E,4E,12E)-13-(benzo[d][1,3]dioxol-5-yl)-N-isobutyltrideca-2,4,12-trienamide
-
-
(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
-
-
(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester
-
treatment with 98 microM resulted in reduction of viable cells from 96.5% (control) to 9.86% after 5 h
(4S)-4-[[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]amino]-5-oxohexanoic acid
1-(2,5-dichlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
-
1-(2-chlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
-
1-(2-fluorobenzyl)-1H-benzimidazol-2-amine
-
-
1-(2-methylbenzyl)-1H-benzimidazol-2-amine
-
-
1-(2-phenylethyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-4-methoxy-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-4-phenyl-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-4-propoxy-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-5,6-dimethyl-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-7-methoxy-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-7-phenyl-1H-benzimidazol-2-amine
-
-
1-(3,4-dichlorobenzyl)-7-propoxy-1H-benzimidazol-2-amine
-
-
1-(3,4-methylenedioxyphenyl)-(1E)-tetradecene
-
-
1-(3,5-dichlorobenzyl)-1H-benzimidazol-2-amine
-
-
1-(3-chlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
-
1-(4-bromobenzyl)-1H-benzimidazol-2-amine
-
-
1-(4-chlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
-
1-(4-methylbenzyl)-1H-benzimidazol-2-amine
-
-
1-(4-tert-butylbenzyl)-1H-benzimidazol-2-amine
-
-
1-(naphthalen-1-ylmethyl)-1H-benzimidazol-2-amine
-
-
1-(naphthalen-2-ylmethyl)-1H-benzimidazol-2-amine
-
-
1-(pyridin-2-yl)-1H-benzimidazol-2-amine
-
-
1-(pyridin-3-yl)-1H-benzimidazol-2-amine
-
-
1-benzyl-2,3-dihydro-1H-benzimidazol-2-amine
-
-
1-ethyl-2,3-dihydro-1H-benzimidazol-2-amine
-
-
1-[(4-[[6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
1-[(4-[[8-amino-3-phenyl-6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
1-[3-(trifluoromethyl)benzyl]-1H-benzimidazol-2-amine
-
-
1H-benzimidazol-2-amine
-
-
2,4,6-triaminoquinazoline
-
i.e. TAQ, mimics the pterin head group of methotrexate, binds to the active site, binding structure and inhibition mechanism
2,4-Diaminopteridines
-
overview
2,4-diaminopyrimidines
2,4-Diaminoquinazolines
-
overview
2,6-dimethyl [3-O-benzyl-1,2-O isopropylidene-beta-L-threo-pentofuronose-4-yl]-1-phenyl-1,4-dihydro pyridine-3,5-dicarboxylic acid diethyl ether
-
-
2,6-dimethyl-4-(3-O-benzyl-1,2-O-isopropylidene-beta-L-threo pentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester
-
oral therapy shows apoptosis like phenotypes targeting pteridine reductase 1 in intracellular amastigotes
2,6-dimethyl-4-(3-O-benzyl-1,2-ortho-isopropylidene-beta-L-threopentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester
-
treatment with 90 microM GDA resulted in reduction of viable cells from 94.2% (control) to 77.1%, 76.8%, 74.9%, 35.3% and 24.9% at 18, 24, 48, 72 and 96 h, respectively
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-thione
2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
2-amino-4-oxo-6-phenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
2-amino-6-(3-formylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
2-amino-6-(4-ethylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
2-amino-6-(4-methoxyphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
2-amino-6-bromo-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-4H-pyrimidin-5-carboxylic acid ethyl ester
-
both monastrol (R) and (S) enantiomers fit well in the ligand-binding pocket of LdPTR1. Monastrol is a potent inhibitor of PTR1 in Leishmania, it inhibits proliferation of amastigotes in macrophage cultures infected with an Leishmania donovani clinical isolate, with no host cytotoxicity
4-(benzyloxy)-1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
-
4-chloro-1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
-
5-Deaza-5,6,7,8-tetrahydrofolate
-
-
6,7-di(propan-2-yl)pteridine-2,4-diamine
6-(benzylsulfanyl)pyrimidine-2,4-diamine
6-methyl-7-(propan-2-yl)pteridine-2,4-diamine
6-phenylpteridine-2,4,7-triamine
6-[(4-methoxybenzyl)sulfanyl]pyrimidine-2,4-diamine
6-[(4-methylphenyl)sulfanyl]pyrimidine-2,4-diamine
7-(benzyloxy)-1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
-
7-chloro-1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
-
dihydrobiopterin
dihydrofolate
dihydroneopterin
-
substrate inhibition
Dihydrosepiapterin
-
substrate inhibition
dimethyl 1-[(4-[[3-(ethoxycarbonyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2,4-dicarboxylate
-
-
dimethyl 1-[(4-[[3-phenyl-7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2,4-dicarboxylate
-
-
ethyl 1-[(4-[[7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2-carboxylate
methotrexate
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]piperidine-4-carboxylate
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl]amino]phenyl)carbonyl]piperidine-4-carboxylate
miltefosine
-
-
N-isobutyl-19-(3',4'-methylenedioxyphenyl)-(2E,4E)-nonadecadienamide
-
-
N4-cyclopropylpyrimidine-2,4,6-triamine
piperlongimin A
-
i.e. (2E)-N-isobutyl-hexadecenamide
piperlongimin B
-
i.e. (2E)-octadecenoylpiperidine
Pteridines
-
and analogs, overview
-
pyrimidine-2,4,6-triamine
quinonoid 6,7-dimethyl-7,8-dihydropterin
quinonoid dihydrobiopterin
sodium antimony gluconate
-
-
trimethoprim
-
-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0032 - 0.0399
biopterin
0.0000294 - 0.033
dihydrobiopterin
0.0034 - 0.0067
dihydrofolate
0.001 - 0.085
folate
0.0014 - 0.0169
NADPH
0.0166 - 0.021
quinonoid 6,7-dimethyl-7,8-dihydropterin
0.0036 - 0.0103
quinonoid dihydrobiopterin
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.22 - 0.23
biopterin
0.05 - 4.7
dihydrobiopterin
0.43 - 0.44
quinonoid 6,7-dimethyl-7,8-dihydropterin
0.54 - 1.84
quinonoid dihydrobiopterin
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
170 - 1700
dihydrobiopterin
21 - 26
quinonoid 6,7-dimethyl-7,8-dihydropterin
160 - 180
quinonoid dihydrobiopterin
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.06
(2-amino-2,3-dihydro-1H-benzimidazol-1-yl)(phenyl)methanone
-
Ki above 0.06 mM, pH and temperature not specified in the publication
0.00011 - 0.00018
(4S)-4-[[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]amino]-5-oxohexanoic acid
0.0037
1-(2,5-dichlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.01
1-(2-chlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.021
1-(2-fluorobenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.015
1-(2-methylbenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.024
1-(2-phenylethyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.06
1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
Ki above 0.06 mM, pH and temperature not specified in the publication
0.0004
1-(3,4-dichlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.00046
1-(3,4-dichlorobenzyl)-4-methoxy-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.06
1-(3,4-dichlorobenzyl)-4-phenyl-1H-benzimidazol-2-amine
-
Ki above 0.06 mM, pH and temperature not specified in the publication
0.00031
1-(3,4-dichlorobenzyl)-4-propoxy-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0039
1-(3,4-dichlorobenzyl)-5,6-dimethyl-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.00065
1-(3,4-dichlorobenzyl)-7-methoxy-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.000007
1-(3,4-dichlorobenzyl)-7-phenyl-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.000047
1-(3,4-dichlorobenzyl)-7-propoxy-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0088
1-(3,5-dichlorobenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0075
1-(3-chlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0031
1-(4-bromobenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0054
1-(4-chlorobenzyl)-2,3-dihydro-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.015
1-(4-methylbenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0042
1-(4-tert-butylbenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0061
1-(naphthalen-1-ylmethyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0028
1-(naphthalen-2-ylmethyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.053
1-(pyridin-2-yl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.054
1-(pyridin-3-yl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.016
1-benzyl-2,3-dihydro-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.2
1-ethyl-2,3-dihydro-1H-benzimidazol-2-amine
-
Ki above 0.2 mM, pH and temperature not specified in the publication
0.007 - 0.075
1-[(4-[[6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
0.02
1-[(4-[[8-amino-3-phenyl-6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
-
-
0.0063
1-[3-(trifluoromethyl)benzyl]-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.228
1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.141
2,4-diaminopyrimidine
-
called compound 3
0.021
2,4-diaminoquinazoline
-
called compound 2
0.027 - 0.035
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
0.035
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-thione
pH 7.5, temperature not specified in the publication, value above 0.035
0.0058 - 0.027
2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
0.00071 - 0.027
2-amino-4-oxo-6-phenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
0.00096 - 0.027
2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
0.0004 - 0.0026
2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
0.00029 - 0.0042
2-amino-6-(3-formylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
0.0005 - 0.0164
2-amino-6-(4-ethylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
0.00036 - 0.0034
2-amino-6-(4-methoxyphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
0.0039 - 0.027
2-amino-6-bromo-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
0.01
2-amino-6-chloro-benzimidazole
-
-
0.000428
4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-4H-pyrimidin-5-carboxylic acid ethyl ester
-
pH 4.8, 30C
0.016
4-(benzyloxy)-1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.0023
4-chloro-1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.00024 - 0.0033
6,7-di(propan-2-yl)pteridine-2,4-diamine
0.0006 - 0.0032
6-(benzylsulfanyl)pyrimidine-2,4-diamine
0.0012 - 0.035
6-methyl-7-(propan-2-yl)pteridine-2,4-diamine
0.0034
6-phenylpteridine-2,4,7-triamine
-
pH 7.5, temperature not specified in the publication
0.0027 - 0.018
6-[(4-methoxybenzyl)sulfanyl]pyrimidine-2,4-diamine
0.0054 - 0.027
6-[(4-methylphenyl)sulfanyl]pyrimidine-2,4-diamine
0.000098
7-(benzyloxy)-1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.00051
7-chloro-1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine
-
pH and temperature not specified in the publication
0.00015 - 0.0038
dihydrobiopterin
0.038
dimethyl 1-[(4-[[3-(ethoxycarbonyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2,4-dicarboxylate
-
-
0.04
dimethyl 1-[(4-[[3-phenyl-7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2,4-dicarboxylate
-
-
0.006 - 0.106
ethyl 1-[(4-[[7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2-carboxylate
0.0000111 - 0.000152
methotrexate
0.000037
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]piperidine-4-carboxylate
-
-
0.0001 - 0.007
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl]amino]phenyl)carbonyl]piperidine-4-carboxylate
0.027 - 0.035
N4-cyclopropylpyrimidine-2,4,6-triamine
0.035
pyrimidine-2,4,6-triamine
pH 7.5, temperature not specified in the publication, value above 0.035
0.0922 - 0.475
quinonoid 6,7-dimethyl-7,8-dihydropterin
0.00122 - 0.00314
quinonoid dihydrobiopterin
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
23.1 - 101
(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
18.3 - 90.8
2,6-dimethyl [3-O-benzyl-1,2-O isopropylidene-beta-L-threo-pentofuronose-4-yl]-1-phenyl-1,4-dihydro pyridine-3,5-dicarboxylic acid diethyl ether
0.01
4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-4H-pyrimidin-5-carboxylic acid ethyl ester
Leishmania donovani
-
pH 4.8, 30C
12.1
sodium antimony gluconate
Leishmania donovani
-
amastigote
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.1
-
pH 3.7, substrate dihydrofolate; pH 3.7, substrate folate
2
-
pH 3.7, substrate biopterin
2.3
-
pH 3.7, substrate dihydrobiopterin
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 7
-
dihydrofolate as substrate
5.5 - 8
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5 - 7
-
pH 4.5: about 50% of maximal activity, pH 7.0: about 30% of maximal activity with biopterin
4.7 - 7
-
significant decline of activity at pH 7 and 4.7
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
in stationary phase promastigotes
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
116000
-
recombinant enzyme, gel filtration
116800
-
gel filtration
117000
-
native enzyme, gel filtration
134000
recombinant enzyme, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
-
x-ray crystallography
tetramer
additional information
x * 57000, SDS-PAGE, GFP-fusion protein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method, using 0.1 M MES pH 6.5, 10%(v/v) dioxane and 1.6 M ammonium sulfate
-
crystallized in complex with reduced cofactor and two different inhibitors
-
enzyme in ternary complex with NADPH and inhibitor 2,4,6-triaminoquinazoline in protein solution containing 10 mg/ml protein, 20 mM sodium acetate, pH 5.3, 1 mM NADPH, 1 mM 2,4,6-triaminoquinazoline, 20 mM DTT, and 1% DMSO, hanging drop vapour diffusion method, against equal volume of 0.002 ml of reservoir solution containing 11-14% PEG 5000, 100 mM sodium acetate, pH 5.5, and 40-140 mM calcium acetate, 20C, thin grew clumps of thin fragile rods, cryopreservation in a solution of 0% reservoir solution and 30% glycerol, X-ray diffraction structure determination and analysis at 2.6 A resolution, molecular replacement
-
in complex with NADPH, and with NADPH and biopterin, 5,6-dihydrobiopterin, or 5,6,7,8-tetrahydrobiopterin as well as in complex with NADPH and inhibitors CB3717 or trimethoprim. Enzyme does not undergo major conformational changes to accomplish binding and processing of substrates. Quinazoline moiety of inhibotr CB3717 binds similarly to pterin of substrate
-
purified recombinant enzyme in binary complex with NADPH and in ternary complex with NADPH and methotrexate, 0.02 ml of protein solution containing 20 mg/ml protein, 20 mM Tris-HCl, pH 7.0, mixed with 0.01 ml of a solution containing 4 mM NADPH, 4 mM methotrexate on ice for 1 h, then mixed with 0.01 ml of reservoir solution containing 28% 1,4-butanediol, 12.5 mM cetyl trimethyl ammonium chloride and 100 mM HEPES, pH 7.0, 5 days, 14C, X-ray diffraction structure determination and analysis of flash frozen crystals at 2.8 A resolution, molecular replacement technique
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, 20% glycerol, 20 mM beta-mercaptoethanol, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HisTrap nickel-chelating column chromatography
-
native and recombinant enzyme
-
recombinant enzyme
recombinant enzyme from Escherichia coli
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3)by nickel affinity chromatography
T7 Tag antibody agarose column chromatography
using Ni-NTA chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed as a His-tagged fusion protein
-
expressed as N-terminal His6-tagged protein in Spodoptera frugiperda 21 cells
-
expressed in Escherichia coli BL21 (DE3) GOLD cells
-
expressed in Escherichia coli strain JM109
expression in Escherichia coli
expression of GFP-tagged enzyme in Leishmania donovani
-
overexpressed in transgenic Leishmania parasites as N-terminal GFP-tagged PTR1-green fluorescent protein
-
overexpression of the N-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3)
promastigote form of Leishmania donovani transfected with GFP and GFP-PTR1 chimera
recombinantly expressed
transgenic parasites overexpress a PTR1-GFP chimera (PTR1 tagged at the N-terminal with GFP)
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K199E
-
The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
Y175D
-
mutant enzyme Y175D shows properties similar to wild type enzyme. The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
Y195F
-
The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
Y195W
-
The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
Y38D
-
The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
pharmacology
-
successful antifolate chemotherapy in Leishmania will have to target simultaneously both pterine reductase 1 and dihydrofolate reductase-thymidylate synthase