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
1.5.1.33
-
RECOMMENDED NAME
GeneOntology No.
pteridine reductase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH + 2 H+
show the reaction diagram
-
-
-
-
5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH + 2 H+
show the reaction diagram
ordered sequential reaction mechanism
-
5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH + 2 H+
show the reaction diagram
ordered ternary complex mechanism with NADPH binding first and NADP+ dissociating after the reduced pteridine. The enzyme transfers the pro-S hydride of NADPH to carbon 6 on the si face of dihydrofolate
-
5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH + 2 H+
show the reaction diagram
conserved residue Tyr194 forms hydrogen bonds with the nucleophilic center of the substrate and stabilizes the transition state, conserved residue Lys198 lowers the pKa of the tyrosine, helps to stabilize the transition state, and may function as proton source for the tyrosine
Q6QDB5
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
EC 1.1.1.253
-
-
formerly
-
H region methotrexate resistance protein
-
-
-
-
NADPH-dependent short-chain dehydrogenase/reductase pteridine reductase
Q6QDB5
-
NADPH-dihydropteridine reductase
-
-
-
-
pteridine reductase
-
-
pteridine reductase 1
-
-
-
-
pteridine reductase 1
-
-
pteridine reductase 1
Q6QDB5
-
pteridine reductase 1
Q6QDB5
broad-spectrum enzyme of pterin and folate metabolism
pteridine reductase 1
A2TEY0
-
pteridine reductase 1
A2TEY0
-
-
pteridine reductase 1
-
-
pteridine reductase 1
O76290
-
pteridine reductase 1
-
-
PTR1
-
-
-
-
PTR1
A2TEY0
-
PTR1
A2TEY0
-
-
reductase, dihydropteridine (reduced nicotinamide adenine dinucleotide phosphate)
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
131384-61-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
clinical isolate
SwissProt
Manually annotated by BRENDA team
clinical isolate
-
-
Manually annotated by BRENDA team
clinical isolate, enzyme is degraded in the stationary phase of growth at the time when the parasites are undergoing metacyclogenesis
SwissProt
Manually annotated by BRENDA team
Y strain
-
-
Manually annotated by BRENDA team
Trypanosoma cruzi Y
Y strain
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
comparisons of isogenic lines shows that ptr1-null mutants are 18fold more sensitive to H2O2 than PTR1-overproducing lines, and significant 3-5fold differences are seen with a broad panel of oxidant-inducing agents
malfunction
-
impossible to generate PTR1 null mutants. RNA interference results in complete knockdown of endogenous protein after 48 h, followed by cell death after 4 days. Lethal phenotype is reversed by expression of PTR1 in RNAi lines or by addition of tetrahydrobiopterin to cultures. Loss of PTR1 is associated with gross morphological changes due to a defect in cytokinesis, resulting in cells with multiple nuclei and kinetoplasts, as well as multiple detached flagella. Electron microscopy also reveal increased numbers of glycosomes, while immunofluorescence microscopy show increased and more diffuse staining for glycosomal matrix enzymes, indicative of mis-localisation to the cytosol. RNAi cell lines are markedly less virulent than wild-type parasites in mice
physiological function
-
using treatment with H2O2 as the selective pressure PTR1 is identified as a mediator of susceptibility to oxidative stress. Oxidant resistance depends upon reduced unconjugated pteridines and PTR1-derived pteridines can modulate oxidant susceptibility
physiological function
-
the enzyme has an essential and dual role in pterin metabolism
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 biopterin + 3 NADPH + 3 H+
dihydrobiopterin + tetrahydrobiopterin + 3 NADP+
show the reaction diagram
Q6QDB5
essential enzyme of pterin and folate metabolism
-
-
?
2 biopterin + 3 NADPH + 3 H+
dihydrobiopterin + tetrahydrobiopterin + 3 NADP+
show the reaction diagram
-
salvage of pterins, enzyme acts as a metabolic bypass for drugs targeting dihydrofolate reductase, PTR1 contributes about 10% of the reduction of folates in wild-type cells while the remaining 90% is due to the activity of dihydrofolate reductase-thymidylate synthase (EC 1.5.1.3)
-
-
?
6-biopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
A2TEY0
-
-
-
?
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
-
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
-
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
-
no activity with NADH and NADP+
-
-
-
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
-
activity with NADH is less than 5% of the activity with NADPH
-
-
-
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
-, P42556
2-step reaction via intermediate 7,8-dihydrobiopterin
-
-
?
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
Trypanosoma cruzi Y
-
no activity with NADH and NADP+
-
-
-
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
-
-
-
-
?
biopterin + NADPH + H+
dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
Dihydrobiopterin + NADPH
?
show the reaction diagram
-
-
-
-
-
Dihydrobiopterin + NADPH
?
show the reaction diagram
-
-
-
-
-
Dihydrobiopterin + NADPH
?
show the reaction diagram
-
-
-
-
-
Dihydrobiopterin + NADPH
?
show the reaction diagram
Trypanosoma cruzi Y
-
-
-
-
-
dihydrobiopterin + NADPH
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
dihydrobiopterin + NADPH
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
O76290
-
-
-
r
dihydrobiopterin + NADPH
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
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
-
-
-
-
?
Dihydrofolate + NADPH
5,6,7,8-Tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
-
Dihydrofolate + NADPH
5,6,7,8-Tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
Dihydrofolate + NADPH
5,6,7,8-Tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
-
Dihydrofolate + NADPH
5,6,7,8-Tetrahydrofolate + NADP+
show the reaction diagram
Trypanosoma cruzi Y
-
-
-
-
-
Dihydroneopterin + NADPH
?
show the reaction diagram
-
-
-
-
-
Dihydroneopterin + NADPH
?
show the reaction diagram
-
no activity
-
-
-
dihydrosepiapterin + NADPH
?
show the reaction diagram
-
-
-
-
-
dihydrosepiapterin + NADPH
?
show the reaction diagram
-
no activity
-
-
-
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
-
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
-
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
-
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
Trypanosoma cruzi Y
-
-
-
-
-
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
-
-
-
-
?
folate + NADPH + H+
7,8-dihydrofolate and tetrahydrofolate + NADP+
show the reaction diagram
Q6QDB5
essential enzyme of pterin and folate metabolism
-
-
?
additional information
?
-
-
no activity with quinoid dihydrobiopterin, primary enzyme mediating pteridine salvage
-
-
-
additional information
?
-
-
the enzyme mediates the synthesis of tetrahydropteridines
-
-
-
additional information
?
-
-
the enzyme is involved in the resistance to the methotrexate, aminopterin and trimethoprim antifolates
-
-
-
additional information
?
-
Q6QDB5
enzyme is associated with folate metabolism, responsible for salvage of pterins and reduction of folates
-
-
-
additional information
?
-
-, P42556
enzyme is used by the organism to bypass antifolate inhibition, catalytic pathway
-
-
-
additional information
?
-
Q6QDB5
NADPH binds first, the enzyme-NADPH complex binds the substrate
-
-
-
additional information
?
-
-
essential for the salvage of pterins
-
-
-
additional information
?
-
Trypanosoma cruzi Y
-
the enzyme is involved in the resistance to the methotrexate, aminopterin and trimethoprim antifolates
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 biopterin + 3 NADPH + 3 H+
dihydrobiopterin + tetrahydrobiopterin + 3 NADP+
show the reaction diagram
Q6QDB5
essential enzyme of pterin and folate metabolism
-
-
?
2 biopterin + 3 NADPH + 3 H+
dihydrobiopterin + tetrahydrobiopterin + 3 NADP+
show the reaction diagram
-
salvage of pterins, enzyme acts as a metabolic bypass for drugs targeting dihydrofolate reductase, PTR1 contributes about 10% of the reduction of folates in wild-type cells while the remaining 90% is due to the activity of dihydrofolate reductase-thymidylate synthase (EC 1.5.1.3)
-
-
?
6-biopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
A2TEY0
-
-
-
?
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
-
-
-
-
?
folate + NADPH + H+
7,8-dihydrofolate and tetrahydrofolate + NADP+
show the reaction diagram
Q6QDB5
essential enzyme of pterin and folate metabolism
-
-
?
additional information
?
-
-
primary enzyme mediating pteridine salvage
-
-
-
additional information
?
-
-
the enzyme mediates the synthesis of tetrahydropteridines
-
-
-
additional information
?
-
-
the enzyme is involved in the resistance to the methotrexate, aminopterin and trimethoprim antifolates
-
-
-
additional information
?
-
Q6QDB5
enzyme is associated with folate metabolism, responsible for salvage of pterins and reduction of folates
-
-
-
additional information
?
-
-, P42556
enzyme is used by the organism to bypass antifolate inhibition, catalytic pathway
-
-
-
additional information
?
-
-
essential for the salvage of pterins
-
-
-
additional information
?
-
Trypanosoma cruzi Y
-
the enzyme is involved in the resistance to the methotrexate, aminopterin and trimethoprim antifolates
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NADPH
-
dependent on
NADPH
-
dependent on
NADPH
-, P42556
binding structure
NADPH
Q6QDB5
binding site is located at residues Gly13 to Arg39, recognition motif GXXXRXG
NADPH
-
dependent on
NADPH
A2TEY0
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2E,4E)-N-isobutyl-dodecenamide
-
-
-
(2E,4E)-N-isobutyl-octadecenamide
-
-
-
(2E,4E,12E,13)-(3,4-methylenedioxyphenyl)-trideca-trienoic acid isobutylamide
-
-
-
(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-(3,4-methylenedioxyphenyl)-(1E)-tetradecene
-
-
-
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
-
-
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
-
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]pyrimidin-4-one
Q581W1
-
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-thione
-
-
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-thione
Q581W1
-
2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
-
2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
-
2-amino-4-oxo-6-phenyl-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
Q581W1
-
2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
-
-
2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
Q581W1
-
2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
-
2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
-
2-amino-6-(3-formylphenyl)-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
Q581W1
-
2-amino-6-(4-ethylphenyl)-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
Q581W1
-
2-amino-6-(4-methoxyphenyl)-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
Q581W1
-
2-amino-6-bromo-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
Q581W1
-
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
5-Deaza-5,6,7,8-tetrahydrofolate
-
-
6,7-di(propan-2-yl)pteridine-2,4-diamine
-
-
6,7-di(propan-2-yl)pteridine-2,4-diamine
Q581W1
-
6-(benzylsulfanyl)pyrimidine-2,4-diamine
-
-
6-(benzylsulfanyl)pyrimidine-2,4-diamine
Q581W1
-
6-methyl-7-(propan-2-yl)pteridine-2,4-diamine
-
-
6-methyl-7-(propan-2-yl)pteridine-2,4-diamine
Q581W1
-
6-phenylpteridine-2,4,7-triamine
-
-
6-phenylpteridine-2,4,7-triamine
Q581W1
-
6-[(4-methoxybenzyl)sulfanyl]pyrimidine-2,4-diamine
-
-
6-[(4-methoxybenzyl)sulfanyl]pyrimidine-2,4-diamine
Q581W1
-
6-[(4-methylphenyl)sulfanyl]pyrimidine-2,4-diamine
-
-
6-[(4-methylphenyl)sulfanyl]pyrimidine-2,4-diamine
Q581W1
-
dihydrobiopterin
-
substrate inhibition above 0.01 mM
dihydrobiopterin
-
substrate inhibition
dihydrobiopterin
-
substrate inhibition
dihydrobiopterin
-
inhibits the enzyme at high substrate concentrations
dihydrofolate
-
substrate inhibition above 0.005 mM
dihydrofolate
-
substrate inhibition
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
-, P42556
binding structure
methotrexate
-
antifolate drug
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
-
-
N-isobutyl-19-(3',4'-methylenedioxyphenyl)-(2E,4E)-nonadecadienamide
-
-
-
N4-cyclopropylpyrimidine-2,4,6-triamine
-
-
N4-cyclopropylpyrimidine-2,4,6-triamine
Q581W1
-
piperlongimin A
-
i.e. (2E)-N-isobutyl-hexadecenamide
-
piperlongimin B
-
i.e. (2E)-octadecenoylpiperidine
-
Pteridines
-
and analogs, overview
-
pyrimidine-2,4,6-triamine
-
-
pyrimidine-2,4,6-triamine
Q581W1
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
-
quinonoid dihydrobiopterin
-
-
sodium antimony gluconate
-
-
trimethoprim
-
-
miltefosine
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
relatively insensitive to methorexate
-
additional information
-
structure-based inhibitor development
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0032
-
biopterin
-
mutant enzyme Y175F
0.0035
-
biopterin
-
wild type enzyme
0.00351
-
biopterin
-
-
0.0101
-
biopterin
-
native enzyme, pH 4.7
0.0109
-
biopterin
-
recombinant enzyme, pH 4.7
0.0116
-
biopterin
-
native enzyme, pH 4.7
0.0122
-
biopterin
-
NADPH, with folate as cosubstrate, recombinant enzyme, pH 6.0; recombinant enzyme, pH 4.7
0.0198
-
biopterin
-
recombinant enzyme, pH 6.0
0.0399
-
biopterin
-
recombinant enzyme, pH 7.0
0.0000294
-
dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.0032
-
dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.0054
-
dihydrobiopterin
-
dihydrofolate, recombinant enzyme, pH 7.0; recombinant enzyme, pH 7.0
0.0056
-
dihydrobiopterin
-
recombinant enzyme, pH 6.0
0.0076
-
dihydrobiopterin
-
recombinant enzyme, pH 4.7
0.0109
-
dihydrobiopterin
-
pH 3.7
0.033
-
dihydrobiopterin
-
-
0.0034
-
dihydrofolate
-
recombinant enzyme, pH 6.0
0.0061
-
dihydrofolate
-
recombinant enzyme, pH 4.7
0.0067
-
dihydrofolate
-
recombinant enzyme, pH 6.0
0.001
-
folate
-
-
0.0016
-
folate
-
recombinant enzyme, pH 4.7
0.0019
-
folate
-
recombinant enzyme, pH 6.0
0.0019
-
folate
-
-
0.0024
-
folate
-
NADPH, with folate as cosubstrate, native enzyme, pH 6.0; native enzyme, pH 6.0
0.0026
-
folate
-
recombinant enzyme, pH 6.0
0.0085
-
folate
-
recombinant enzyme, pH 7.0
0.0085
-
folate
-
dihydrobiopterin, recombinant enzyme, pH 4.7
0.0014
-
NADPH
-
with folate as cosubstrate
0.00935
-
NADPH
-
with dihydrobiopterin as cosubstrate, recombinant enzyme, pH 4.7
0.012
-
NADPH
-
with dihydrofolate as cosubstrate, recombinant enzyme, pH 6.0
0.012
-
NADPH
-
NADPH
0.0123
-
NADPH
-
with biopterin as cosubstrate, recombinant enzyme, pH 4.7
0.0132
-
NADPH
-
with biopterin as cosubstrate, recombinant enzyme, pH 4.7
0.0142
-
NADPH
-
with dihydrofolate as cosubstrate, recombinant enzyme, pH 6.0
0.0145
-
NADPH
-
with dihydrobiopterin as cosubstrate, recombinant enzyme, pH 4.7
0.0146
-
NADPH
-
with folate as cosubstrate, recombinant enzyme, pH 6.0
0.0166
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.021
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.0036
-
quinonoid dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.0103
-
quinonoid dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.22
-
biopterin
-
mutant enzyme Y175F
0.23
-
biopterin
-
wild type enzyme
0.05
-
dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.57
-
dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
4.7
-
dihydrobiopterin
-
pH 3.7
0.43
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.44
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.54
-
quinonoid dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
1.84
-
quinonoid dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
170
-
dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
9809
1700
-
dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
9809
21
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
332806
26
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
332806
160
-
quinonoid dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
26417
180
-
quinonoid dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
26417
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00011
-
(4S)-4-[[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]amino]-5-oxohexanoic acid
-
-
0.00018
-
(4S)-4-[[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]amino]-5-oxohexanoic acid
-
-
0.007
-
1-[(4-[[6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
-
-
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
-
-
0.141
-
2,4-diaminopyrimidine
-
called compound 3
0.021
-
2,4-diaminoquinazoline
-
called compound 2
0.027
-
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
-
pH 7.5, temperature not specified in the publication, value above 0.027
0.035
-
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
Q581W1
pH 7.5, temperature not specified in the publication, value above 0.035
0.027
-
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-thione
-
pH 7.5, temperature not specified in the publication, value above 0.027
0.035
-
2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-thione
Q581W1
pH 7.5, temperature not specified in the publication, value above 0.035
0.0058
-
2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
pH 7.5, temperature not specified in the publication
0.027
-
2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
pH 7.5, temperature not specified in the publication, value above 0.027
0.00071
-
2-amino-4-oxo-6-phenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
pH 7.5, temperature not specified in the publication
0.027
-
2-amino-4-oxo-6-phenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
pH 7.5, temperature not specified in the publication, value above 0.027
0.00096
-
2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
Q581W1
pH 7.5, temperature not specified in the publication
0.027
-
2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
-
pH 7.5, temperature not specified in the publication, value above 0.027
0.0004
-
2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
pH 7.5, temperature not specified in the publication
0.0026
-
2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
pH 7.5, temperature not specified in the publication
0.00029
-
2-amino-6-(3-formylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
pH 7.5, temperature not specified in the publication
0.0042
-
2-amino-6-(3-formylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
pH 7.5, temperature not specified in the publication
0.0005
-
2-amino-6-(4-ethylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
pH 7.5, temperature not specified in the publication
0.0164
-
2-amino-6-(4-ethylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
pH 7.5, temperature not specified in the publication
0.00036
-
2-amino-6-(4-methoxyphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
pH 7.5, temperature not specified in the publication
0.0034
-
2-amino-6-(4-methoxyphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
pH 7.5, temperature not specified in the publication
0.0039
-
2-amino-6-bromo-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
Q581W1
pH 7.5, temperature not specified in the publication
0.027
-
2-amino-6-bromo-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
pH 7.5, temperature not specified in the publication, value above 0.027
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
0.00024
-
6,7-di(propan-2-yl)pteridine-2,4-diamine
-
pH 7.5, temperature not specified in the publication
0.0033
-
6,7-di(propan-2-yl)pteridine-2,4-diamine
Q581W1
pH 7.5, temperature not specified in the publication
0.0006
-
6-(benzylsulfanyl)pyrimidine-2,4-diamine
-
pH 7.5, temperature not specified in the publication
0.0032
-
6-(benzylsulfanyl)pyrimidine-2,4-diamine
Q581W1
pH 7.5, temperature not specified in the publication
0.0012
-
6-methyl-7-(propan-2-yl)pteridine-2,4-diamine
-
pH 7.5, temperature not specified in the publication
0.035
-
6-methyl-7-(propan-2-yl)pteridine-2,4-diamine
Q581W1
pH 7.5, temperature not specified in the publication, value above 0.035
0.0012
-
6-phenylpteridine-2,4,7-triamine
Q581W1
pH 7.5, temperature not specified in the publication
0.0034
-
6-phenylpteridine-2,4,7-triamine
-
pH 7.5, temperature not specified in the publication
0.0027
-
6-[(4-methoxybenzyl)sulfanyl]pyrimidine-2,4-diamine
-
pH 7.5, temperature not specified in the publication
0.018
-
6-[(4-methoxybenzyl)sulfanyl]pyrimidine-2,4-diamine
Q581W1
pH 7.5, temperature not specified in the publication
0.0054
-
6-[(4-methylphenyl)sulfanyl]pyrimidine-2,4-diamine
Q581W1
pH 7.5, temperature not specified in the publication
0.027
-
6-[(4-methylphenyl)sulfanyl]pyrimidine-2,4-diamine
-
pH 7.5, temperature not specified in the publication, value above 0.027
0.00015
-
dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.00116
-
dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.0038
-
dihydrobiopterin
-
pH 3.7
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
-
ethyl 1-[(4-[[7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2-carboxylate
-
-
0.106
-
ethyl 1-[(4-[[7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2-carboxylate
-
-
0.0000111
-
methotrexate
-
-
0.000039
-
methotrexate
-
pH and temperature not specified in the publication
0.000152
-
methotrexate
-
pH 3.7
0.000037
-
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]piperidine-4-carboxylate
-
-
0.0001
-
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl]amino]phenyl)carbonyl]piperidine-4-carboxylate
-
-
0.007
-
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl]amino]phenyl)carbonyl]piperidine-4-carboxylate
-
-
0.027
-
N4-cyclopropylpyrimidine-2,4,6-triamine
-
pH 7.5, temperature not specified in the publication, value above 0.027
0.035
-
N4-cyclopropylpyrimidine-2,4,6-triamine
Q581W1
pH 7.5, temperature not specified in the publication, value above 0.035
0.027
-
pyrimidine-2,4,6-triamine
-
pH 7.5, temperature not specified in the publication, value above 0.027
0.035
-
pyrimidine-2,4,6-triamine
Q581W1
pH 7.5, temperature not specified in the publication, value above 0.035
0.0922
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.475
-
quinonoid 6,7-dimethyl-7,8-dihydropterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.00122
-
quinonoid dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
0.00314
-
quinonoid dihydrobiopterin
-
in 50 mM HEPES buffer, pH 7.4, at 25C
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
23.1
-
(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
-
amastigote
101
-
(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
-
promastigote
18.3
-
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
-
amastigote
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
-
promastigote
0.01
-
4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-4H-pyrimidin-5-carboxylic acid ethyl ester
-
pH 4.8, 30C
12.1
-
sodium antimony gluconate
-
amastigote
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.7
-
-
biopterin as substrate; dihydrobiopterin as substrate
4.7
-
-
biopterin as substrate
4.7
-
-
biopterin as substrate; dihydrobiopterin as substrate
5
7
-
dihydrofolate as substrate
6
-
-
folate as substrate
6
-
-
biopterin as substrate
6
-
-
folate as substrate
6
-
-
dihydrofolate as substrate; folate as substrate
6
-
-
biopterin as substrate
7.5
-
-
assay at
7.5
-
Q581W1
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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 ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Q6QDB5
in stationary phase promastigotes
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
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
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
116000
-
-
recombinant enzyme, gel filtration
116800
-
-
gel filtration
117000
-
-
native enzyme, gel filtration
134000
-
Q6QDB5
recombinant enzyme, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 30000, calculation from nucleotide sequence
?
A2TEY0
x * 51000, SDS-PAGE
?
-
x * 51000, SDS-PAGE
-
?
Trypanosoma cruzi Y
-
x * 30000, calculation from nucleotide sequence
-
tetramer
-
4 * 30000, SDS-PAGE
tetramer
-
4 * 30000
tetramer
-
2 * 31000, SDS-PAGE
tetramer
-, P42556
structure analysis
tetramer
-
4 * 25700, crystal structure
tetramer
Q6QDB5
4 * 33500, recombinant enzyme, SDS-PAGE, 4 * 29000, native enzyme, SDS-PAGE
tetramer
-
crystallization data
tetramer
Q6QDB5
-
homotetramer
-
x-ray crystallography
additional information
Q6QDB5
x * 57000, SDS-PAGE, GFP-fusion protein
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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
-, P42556
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, 20% glycerol, 20 mM beta-mercaptoethanol, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
HisTrap nickel-chelating column chromatography
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3)by nickel affinity chromatography
Q6QDB5
using Ni-NTA chromatography
-
native and recombinant enzyme
-
T7 Tag antibody agarose column chromatography
A2TEY0
recombinant enzyme
-
recombinant enzyme from Escherichia coli
-, P42556
recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed as a His-tagged fusion protein
-
expressed in Escherichia coli BL21 (DE3) GOLD cells
-
expression of GFP-tagged enzyme in Leishmania donovani
-
overexpressed in transgenic Leishmania parasites as N-terminal GFP-tagged PTR1-green fluorescent protein
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overexpression of the N-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3)
Q6QDB5
promastigote form of Leishmania donovani transfected with GFP and GFP-PTR1 chimera
Q6QDB5
expression in Escherichia coli
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recombinantly expressed
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transgenic parasites overexpress a PTR1-GFP chimera (PTR1 tagged at the N-terminal with GFP)
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expressed in Escherichia coli strain JM109
A2TEY0
expression in Escherichia coli
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expressed as N-terminal His6-tagged protein in Spodoptera frugiperda 21 cells
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recombinantly expressed
Q581W1
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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 ACCESSION NO.
COMMENTARY
LITERATURE
drug development
-
target for antifolate chemotherapy against Leishmania
medicine
Q6QDB5
enzyme is an important chemotherapeutic target for drugs against Leishmania
drug development
-
target for antiparasite drug development
medicine
-
enzyme is a target for development of improved therapies for infection by trypanosomatid parasites
pharmacology
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successful antifolate chemotherapy in Leishmania will have to target simultaneously both pterine reductase 1 and dihydrofolate reductase-thymidylate synthase
drug development
-
target for antiparasite drug development