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Information on EC 1.5.1.3 - dihydrofolate reductase and Organism(s) Plasmodium falciparum and UniProt Accession P13922

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EC Tree
     1 Oxidoreductases
         1.5 Acting on the CH-NH group of donors
             1.5.1 With NAD+ or NADP+ as acceptor
                1.5.1.3 dihydrofolate reductase
IUBMB Comments
The enzyme from animals and some micro-organisms also slowly reduces folate to 5,6,7,8-tetrahydrofolate.
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Select one or more organisms in this record: ?
This record set is specific for:
Plasmodium falciparum
UNIPROT: P13922
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Word Map
The taxonomic range for the selected organisms is: Plasmodium falciparum
The enzyme appears in selected viruses and cellular organisms
Synonyms
dhfr, dihydrofolate reductase, thy-1, dhfr-ts, hdhfr, dihydrofolate reductase-thymidylate synthase, ecdhfr, pcdhfr, r67 dhfr, ts-dhfr, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7,8-dihydrofolate reductase
-
-
-
-
dehydrogenase, tetrahydrofolate
-
-
-
-
DHFR type IIIC
-
-
-
-
dihydrofolate reductase
-
-
dihydrofolate reductase-thymidylate synthase
-
-
-
-
dihydrofolate reductase:thymidylate synthase
-
-
-
-
dihydrofolic acid reductase
-
-
-
-
dihydrofolic reductase
-
-
-
-
folic acid reductase
-
-
-
-
folic reductase
-
-
-
-
NADPH-dihydrofolate reductase
-
-
-
-
pteridine reductase:dihydrofolate reductase
-
-
-
-
reductase, dihydrofolate
-
-
-
-
tetrahydrofolate dehydrogenase
-
-
-
-
thymidylate synthetase-dihydrofolate reductase
-
-
-
-
Trimethoprim resistance protein
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
show the reaction diagram
in Plasmodium bifunctional thymidylate synthase-dihydrofolate reductase, the overall rate-limiting step is thymidylate synthase catalysis.If thymidylate synthase is in an activated liganded conformation, the dihydrofolate reductase is 2-fold activated. The thymidylate synthase rate is also reciprocally activated by 1.5-fold if dihydrolfolate reductase is in an activated, ligand-bound conformation
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase
The enzyme from animals and some micro-organisms also slowly reduces folate to 5,6,7,8-tetrahydrofolate.
CAS REGISTRY NUMBER
COMMENTARY hide
9002-03-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyrimethamine
(1E)-1-[4-[(3,5-dichloropyridin-4-yl)oxy]phenyl]ethanone thiosemicarbazone
-
-
1,1'-{6-[(4-nitrophenyl)amino]-1,3,5-triazine-2,4-diyl}bis(4-benzylpyrazinediium)
-
minimal inhibitory concentration: 0.003536 mM
1,1'-{6-[(4-nitrophenyl)amino]-1,3,5-triazine-2,4-diyl}bis(4-methylpyrazinediium)
-
minimal inhibitory concentration: 0.002418 mM
1,1'-{6-[(4-nitrophenyl)amino]-1,3,5-triazine-2,4-diyl}bis(4-phenylpyrazinediium)
-
minimal inhibitory concentration: 0.018 mM
1-(4-chlorophenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
-
1-[3-(3,4-dichlorophenoxy)propyloxy]-5-isopropylbiguanide
-
i.e. PS-16
1-[3-(4-chlorophenoxy)propyloxy]-5-isopropylbiguanide
-
i.e. PS-33
2,2'-({6-[(4-nitrophenyl)amino]-1,3,5-triazine-2,4-diyl}diimino)diethanol
-
minimal inhibitory concentration: 0.149 mM
2,3-bis(hydrazino)quinoxaline
-
-
2-[[(4-[[(2-amino-4-oxo-3,4-dihydropyrido[3,2-d]pyrimidin-6-yl)methyl]amino]phenyl)carbonyl]amino]hexanedioic acid
-
-
2-[[1-(3-chlorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl]carbonyl]-N-prop-2-en-1-ylhydrazinecarbothioamide
-
-
3-[[(4-chlorophenyl)sulfonyl]methyl]-N'-hydroxybenzenecarboximidamide
-
-
4,6-di(5,8-dihydro-1,7-naphthyridin-7(6H)-yl)-N-(4-nitrophenyl)-1,3,5-triazin-2-amine
-
minimal inhibitory concentration: 0.020 mM
4,6-di(morpholin-4-yl)-N-(4-nitrophenyl)-1,3,5-triazin-2-amine
-
minimal inhibitory concentration: 0.0258 mM
4-(benzyloxy)benzaldehyde thiosemicarbazone
-
-
4-chloro-N-[4-(hydroxycarbamimidoyl)benzyl]benzamide
-
-
4-[(3,5-dichloropyridin-4-yl)oxy]-N'-hydroxybenzenecarboximidamide
-
-
4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy]benzaldehyde thiosemicarbazone
-
-
5-(3,4-dichlorophenyl)-6-ethylpyrimidine-2,4-diamine
-
-
5-(3-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
-
-
5-(4-bromophenyl)-6-ethylpyrimidine-2,4-diamine
-
-
5-(4-chlorophenyl)-6-(4-methoxyphenyl)pyrimidine-2,4-diamine
-
-
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
-
-
5-(4-chlorophenyl)-6-isobutylpyrimidine-2,4-diamine
-
-
5-(4-chlorophenyl)-6-isopropylpyrimidine-2,4-diamine
-
-
5-(4-chlorophenyl)-6-phenylpyrimidine-2,4-diamine
-
-
5-(4-chlorophenyl)-6-propylpyrimidine-2,4-diamine
-
-
6-ethyl-5-(4-methoxyphenyl)pyrimidine-2,4-diamine
-
-
6-[[(2,5-dimethylphenyl)amino]methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine
6-[[(3,4-dimethoxyphenyl)amino]methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine
-
-
benzaldehyde semicarbazone
-
-
chlorocycloguanil
-
-
Chloroquine
-
-
cycloguanil
methotrexate
-
-
methyl 4-(2,6-diamino-5-phenylpyrimidin-4-yl)butanoate
-
-
methyl 4-[2,6-diamino-5-(3-chlorophenyl)pyrimidin-4-yl]butanoate
-
-
methyl 5-[(1E)-N-carbamoylethanehydrazonoyl]-2,3'-bithiophene-5'-carboxylate
-
-
N-(4-nitrophenyl)-4,6-di(piperidin-1-yl)-1,3,5-triazin-2-amine
-
minimal inhibitory concentration: 0.130 mM
N-(4-nitrophenyl)-4,6-di(pyrrolidin-1-yl)-1,3,5-triazin-2-amine
-
minimal inhibitory concentration: 0.140 mM
N2,N2,N4,N4-tetraethyl-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.027 mM
N2,N4-bis(3-fluorophenyl)-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.022968 mM
N2,N4-bis[2-(morpholin-4-yl)ethyl]-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.0042 mM
N2,N4-bis[3-(1H-imidazol-1-yl)propyl]-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.0021 mM
N2,N4-bis[3-(morpholin-4-yl)propyl]-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.0039 mM
N2,N4-di-tert-butyl-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.139 mM
N2,N4-dibenzyl-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.023393 mM
N2,N4-dibutyl-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.0055 mM
N2,N4-dicycloheptyl-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.0041 mM
N2,N4-dicyclohexyl-N6-(4-nitrophenyl)-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.0024 mM
N2-(4-nitrophenyl)-N4,N6-dioctyl-1,3,5-triazine-2,4,6-triamine
-
minimal inhibitory concentration: 0.021 mM
NCI0086195
-
docking analysis, overview
NCI0109835
-
docking analysis, overview
NCI0156252
-
docking analysis, overview
NCI0164641
-
docking analysis, overview
NCI0211175
-
docking analysis, overview
NCI0289533
-
docking analysis, overview
NCI0289541
-
docking analysis, overview
NCI0309401
-
docking analysis, overview
NCI0369769
-
docking analysis, overview
NCI0696662
-
docking analysis, overview
pyrimethamine
triclosan
-
specifically targets both wild-type and pyrimethamine-resistant Plasmodium falciparum dihydrofolate reductases and selectively inhibits both the wild-type and pyrimethamine-resistant enzymes compared to human DHFR
trimepthoprim
-
-
WR99210
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0042 - 0.0086
7,8-dihydrofolate
0.0043 - 0.0105
NADPH
0.005 - 0.05
7,8-dihydrofolate
0.0027 - 0.052
NADPH
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2 - 92
7,8-dihydrofolate
2.8 - 60.9
NADPH
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00000024 - 0.0000018
cycloguanil
0.00000012 - 0.0000012
pyrimethamine
0.000001 - 0.0000534
5-(3,4-dichlorophenyl)-6-ethylpyrimidine-2,4-diamine
0.0000008 - 0.0000033
5-(3-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
0.0000003 - 0.000303
5-(4-bromophenyl)-6-ethylpyrimidine-2,4-diamine
0.0000043 - 0.001576
5-(4-chlorophenyl)-6-(4-methoxyphenyl)pyrimidine-2,4-diamine
0.0000003 - 0.000385
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
0.0000003 - 0.000798
5-(4-chlorophenyl)-6-isobutylpyrimidine-2,4-diamine
0.0000003 - 0.000541
5-(4-chlorophenyl)-6-isopropylpyrimidine-2,4-diamine
0.0000029 - 0.003461
5-(4-chlorophenyl)-6-phenylpyrimidine-2,4-diamine
0.0000005 - 0.000359
5-(4-chlorophenyl)-6-propylpyrimidine-2,4-diamine
0.0000009 - 0.000617
6-ethyl-5-(4-methoxyphenyl)pyrimidine-2,4-diamine
0.000001 - 0.000158
cycloguanil
0.0000006 - 0.0000241
methyl 4-(2,6-diamino-5-phenylpyrimidin-4-yl)butanoate
0.0000005 - 0.0000028
methyl 4-[2,6-diamino-5-(3-chlorophenyl)pyrimidin-4-yl]butanoate
0.00000072 - 0.000514
pyrimethamine
0.00000044 - 0.0000155
WR99210
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00001 - 0.00347
pyrimethamine
0.00005 - 0.00092
WR99210
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.6 - 0.7
-
recombinant mutants S108V and S108M
0.82
-
wild-type, 25°C, pH 7.0
1
-
recombinant mutants S108C and S108L
17
-
recombinant wild-type enzyme
2
-
recombinant mutant S108A
4
-
recombinant mutant S108G
5
-
recombinant mutant S108Q
8
-
recombinant mutant S108T
9
-
recombinant mutant S108N
additional information
-
coupled radiometric assay
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 6.5
-
mutant W48Y, more than 60% of maximum activity
4 - 7.5
-
wild-type, more than 60% of maximum activity
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
a major band at 35000 Da and minor bands at 35000 Da and 42000 Da detected on SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CoMFA and quantum chemical calculations studies on pyrimethamine derivatives active against quadruple mutant N5I/C59R/S108N/I164L. Residue N108 is the cause of pyrimethamine resistance with the highest repulsive interaction energy
modeling of 31 pyrimethamine derivatives into the active site of dihydrofolate reductase obtained from crystal structures 1J3I.pdb and 1J3K.pdb. Evaluation of predicted binding modes and key protein-ligand interactions
modeling of 32 pyrimethamine derivatives into the active site of dihydrofolate reductase obtained from crystal structure 1J3K.pdb. Evaluation of predicted binding modes and key protein-ligand interactions
-
modified microbatch method with PRG 4000 as the primary precipitating agent, crystals belong to the orthorhombic space group P2(1)2(1)2(1), with two molecules per asymmetric unit and 52% solvent content
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K27E
kinetic properties similar to wild-type, increase in solubility
N5I/C59R/S108N/I164L
naturally occuring mutant. Residue N108 is the cause of pyrimethamine resistance with the highest repulsive interaction energy
Y35G/F37L
kinetic properties similar to wild-type, increase in solubility
Y35L/F37R
kinetic properties similar to wild-type, increase in solubility
Y35L/F37T
kinetic properties similar to wild-type, increase in solubility
Y35Q/F37R
kinetic properties similar to wild-type, increase in solubility
A16V
-
point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine
A16V/N51I/C59R/S108N
-
point mutations of the active site residues lead to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine, binding structure modelling, overview
C59R
-
point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine
C59R/S108N
I164L
-
mutation I164L is not associated with high-level sulfadoxine-pyrimethamine resistance or poor outcome among infected adults living where malaria is highly endemic
I164X
-
point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine
I51N/C59R/N108S/I164L
-
mutant isolated in an effort to mimic the impact of drug pressure on the selection of dihydrofolate reductase mutations in the malaria parasite population, based on DHFR-TS-QM mutation which exhibits the highest degree of antifolate resistance developed in the field
N51I
-
point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine
N51I/C59R/N108S/I164L
-
mutant isolated in an effort to mimic the impact of drug pressure on the selection of dihydrofolate reductase mutations in the malaria parasite population, based on DHFR-TS-QM mutation which exhibits the highest degree of antifolate resistance developed in the field
N51I/C59R/N108T/I164L
-
mutant isolated in an effort to mimic the impact of drug pressure on the selection of dihydrofolate reductase mutations in the malaria parasite population, based on DHFR-TS-QM mutation which exhibits the highest degree of antifolate resistance developed in the field
N51I/C59R/S108N
N51I/C59R/S108N/I164L
N51I/C59R/S108N/I164L/D187A
-
mutant isolated in an effort to mimic the impact of drug pressure on the selection of dihydrofolate reductase mutations in the malaria parasite population, based on DHFR-TS-QM mutation which exhibits the highest degree of antifolate resistance developed in the field
N51I/C59R/S108N/I164L/I150V/N182I/N201D
-
mutant isolated in an effort to mimic the impact of drug pressure on the selection of dihydrofolate reductase mutations in the malaria parasite population, based on DHFR-TS-QM mutation which exhibits the highest degree of antifolate resistance developed in the field
N51I/C59R/S108N/I164L/K96N
-
mutant isolated in an effort to mimic the impact of drug pressure on the selection of dihydrofolate reductase mutations in the malaria parasite population, based on DHFR-TS-QM mutation which exhibits the highest degree of antifolate resistance developed in the field
S108A
-
combinatorial mutagenesis
S108C
-
combinatorial mutagenesis
S108D
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
S108E
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
S108F
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
S108G
-
combinatorial mutagenesis
S108H
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
S108I
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
S108L
-
combinatorial mutagenesis, reduced activity
S108M
-
combinatorial mutagenesis, reduced activity
S108N
S108N/C59R
-
natural mutants isolated in a study on the association between the clinical and parasitological response to sulfadoxinepyrimethamine and allelic combinations of dihydrofolate reductase and dihydropteroate synthase genes
S108N/N51I
-
natural mutants isolated in a study on the association between the clinical and parasitological response to sulfadoxinepyrimethamine and allelic combinations of dihydrofolate reductase and dihydropteroate synthase genes
S108P
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
S108Q
-
combinatorial mutagenesis, reduced activity, conferred resistance to pyrimethamine and cycloguanil
S108R
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
S108T
S108V
-
combinatorial mutagenesis, reduced activity
S108W
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
S108Y
-
combinatorial mutagenesis, no detectable activity on refolding from inclusion bodies
W48Y
-
3% of wild-type activity
W48Y/N188Y
-
28.9% of wild-type activity
additional information
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 20 mM potassium phosphate, pH 7.0, 0.1 mM EDTA, 10 mM dithiothreitol, 0.2 M KCl, 20% glycerol, mutant S108Q loss of 40% activity after 7 months
-
-20°C, 20 mM potassium phosphate, pH7.0, 0.1 mM EDTA, 10 mM dithiothreitol, 0.2 M KCl, 20% glycerol, mutants S108G, S108A and S108C stable over 7 months
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
wild-type enzyme readily aggregates at 2 mg/ml
refolding and purification of wild-type and mutant enzymes from inclusion bodies in Escherichia coli
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
expression in Escherichia coli BL21 (DE3) pLysS
-
expression of wild-type and mutant enzymes in Escherichia coli
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
refolding of recombinant enzymes from inclusion bodies due to expression in E. coli
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
in vivo screening system to select for functionally active proteins with increased solubility. Fusion of enzyme to green fluorescent protein as reporter for solubility
drug development
modeling of 31 pyrimethamine derivatives into the active site of dihydrofolate reductase obtained from crystal structures 1J3I.pdb and 1J3K.pdb. Evaluation of predicted binding modes and key protein-ligand interactions
analysis
-
heteroduplex tracking assay to detect dihydrofolate redctase L164-mutations in variants representing 1% of the parasites in an individual host
biotechnology
-
method for screening combinatorial or other libraries of Plasmodium falciparum enzyme based on affinities of the inhibitors with the enzyme
drug development
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Reyes, P.; Rathod, P.K.
Dihydrofolate reductase: a coupled radiometric assay
Methods Enzymol.
122
360-367
1986
Bos taurus, Plasmodium falciparum
Manually annotated by BRENDA team
Sirawaraporn, W.; Yongkiettrakul, S.; Sirawaraporn, R.; Yuthavong, Y.; Santi, D.V.
Plasmodium falciparum: asparagine mutant at residue 108 of dihydrofolate reductase is an optimal antifolate-resistant single mutant
Exp. Parasitol.
87
245-252
1997
Plasmodium falciparum
Manually annotated by BRENDA team
Chitnumsub, P.; Yuvaniyama, J.; Vanichtanankul, J.; Kamchonwongpaisan, S.; Walkinshaw, M.D.; Yuthavong, Y.
Characterization, crystallization and preliminary X-ray analysis of bifunctional dihydrofolate reductase-thymidylate synthase from Plasmodium falciparum
Acta Crystallogr. Sect. D
60
780-783
2004
Plasmodium falciparum
Manually annotated by BRENDA team
Kamchonwongpaisan, S.; Vanichtanankul, J.; Tarnchompoo, B.; Yuvaniyama, J.; Taweechai, S.; Yuthavong, Y.
Stoichiometric selection of tight-binding inhibitors by wild-type and mutant forms of malarial (Plasmodium falciparum) dihydrofolate reductase
Anal. Chem.
77
1222-1227
2005
Homo sapiens, Plasmodium falciparum
Manually annotated by BRENDA team
Djaman, J.A.; Mazabraud, A.; Basco, L.
Sulfadoxine-pyrimethamine susceptibilities and analysis of the dihydrofolate reductase and dihydropteroate synthase of Plasmodium falciparum isolates from Cote d'Ivoire
Ann. Trop. Med. Parasitol.
101
103-112
2007
Plasmodium falciparum
Manually annotated by BRENDA team
Ahmed, A.; Das, M.K.; Dev, V.; Saifi, M.A.; Wajihullah, M.A.; Sharma, Y.D.
Quadruple mutations in dihydrofolate reductase of Plasmodium falciparum isolates from Car Nicobar Island, India
Antimicrob. Agents Chemother.
50
1546-1549
2006
Plasmodium falciparum
Manually annotated by BRENDA team
Japrung, D.; Chusacultanachai, S.; Yuvaniyama, J.; Wilairat, P.; Yuthavong, Y.
A simple dual selection for functionally active mutants of Plasmodium falciparum dihydrofolate reductase with improved solubility
Protein Eng. Des. Sel.
18
457-464
2005
Plasmodium falciparum (P13922), Plasmodium falciparum
Manually annotated by BRENDA team
Tahar, R.; Basco, L.K.
Molecular epidemiology of malaria in Cameroon. XXVII. Clinical and parasitological response to sulfadoxine-pyrimethamine treatment and Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase alleles in Cameroonian children
Acta Trop.
103
81-89
2007
Plasmodium falciparum
Manually annotated by BRENDA team
Raman, J.; Sharp, B.; Kleinschmidt, I.; Roper, C.; Streat, E.; Kelly, V.; Barnes, K.I.
Differential effect of regional drug pressure on dihydrofolate reductase and dihydropteroate synthetase mutations in southern Mozambique
Am. J. Trop. Med. Hyg.
78
256-261
2008
Plasmodium falciparum
Manually annotated by BRENDA team
Juliano, J.J.; Trottman, P.; Mwapasa, V.; Meshnick, S.R.
Detection of the dihydrofolate reductase-164L mutation in Plasmodium falciparum infections from Malawi by heteroduplex tracking assay
Am. J. Trop. Med. Hyg.
78
892-894
2008
Plasmodium falciparum
Manually annotated by BRENDA team
Japrung, D.; Leartsakulpanich, U.; Chusacultanachai, S.; Yuthavong, Y.
Conflicting requirements of Plasmodium falciparum dihydrofolate reductase mutations conferring resistance to pyrimethamine-WR99210 combination
Antimicrob. Agents Chemother.
51
4356-4360
2007
Plasmodium falciparum
Manually annotated by BRENDA team
Dasgupta, T.; Anderson, K.S.
Probing the role of parasite-specific, distant structural regions on communication and catalysis in the bifunctional thymidylate synthase-dihydrofolate reductase from Plasmodium falciparum
Biochemistry
47
1336-1345
2008
Plasmodium falciparum (P13922), Plasmodium falciparum
Manually annotated by BRENDA team
Kamchonwongpaisan, S.; Vanichtanankul, J.; Taweechai, S.; Chitnumsub, P.; Yuthavong, Y.
The role of tryptophan-48 in catalysis and binding of inhibitors of Plasmodium falciparum dihydrofolate reductase
Int. J. Parasitol.
37
787-793
2007
Plasmodium falciparum
Manually annotated by BRENDA team
Fogel, G.B.; Cheung, M.; Pittman, E.; Hecht, D.
Modeling the inhibition of quadruple mutant Plasmodium falciparum dihydrofolate reductase by pyrimethamine derivatives
J. Comput. Aided Mol. Des.
22
29-38
2008
Plasmodium falciparum
Manually annotated by BRENDA team
Maitarad, P.; Saparpakorn, P.; Hannongbua, S.; Kamchonwongpaisan, S.; Tarnchompoo, B.; Yuthavong, Y.
Particular interaction between pyrimethamine derivatives and quadruple mutant type dihydrofolate reductase of Plasmodium falciparum: CoMFA and quantum chemical calculations studies
J. Enzyme Inhib. Med. Chem.
24
471-479
2008
Plasmodium falciparum (P13922), Plasmodium falciparum
Manually annotated by BRENDA team
Fogel, G.B.; Cheung, M.; Pittman, E.; Hecht, D.
In silico screening against wild-type and mutant Plasmodium falciparum dihydrofolate reductase
J. Mol. Graph. Model.
26
1145-1152
2008
Plasmodium falciparum (P13922), Plasmodium falciparum
Manually annotated by BRENDA team
A-Elbasit, I.E.; Alifrangis, M.; Khalil, I.F.; Bygbjerg, I.C.; Masuadi, E.M.; Elbashir, M.I.; Giha, H.A.
The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics
Malar. J.
6
108
2007
Plasmodium falciparum
Manually annotated by BRENDA team
Fernandes, N.; Figueiredo, P.; do Rosario, V.E.; Cravo, P.
Analysis of sulphadoxine/pyrimethamine resistance-conferring mutations of Plasmodium falciparum from Mozambique reveals the absence of the dihydrofolate reductase 164L mutant
Malar. J.
6
35
2007
Plasmodium falciparum
Manually annotated by BRENDA team
Sandefur, C.I.; Wooden, J.M.; Quaye, I.K.; Sirawaraporn, W.; Sibley, C.H.
Pyrimethamine-resistant dihydrofolate reductase enzymes of Plasmodium falciparum are not enzymatically compromised in vitro
Mol. Biochem. Parasitol.
154
1-5
2007
Plasmodium falciparum
Manually annotated by BRENDA team
Hamel, M.J.; Poe, A.; Bloland, P.; McCollum, A.; Zhou, Z.; Shi, Y.P.; Ouma, P.; Otieno, K.; Vulule, J.; Escalante, A.; Udhayakumar, V.; Slutsker, L.
Dihydrofolate reductase I164L mutations in Plasmodium falciparum isolates: clinical outcome of 14 Kenyan adults infected with parasites harbouring the I164L mutation
Trans. R. Soc. Trop. Med. Hyg.
102
338-345
2008
Plasmodium falciparum
Manually annotated by BRENDA team
Adane, L.; Patel, D.S.; Bharatam, P.V.
Shape- and chemical feature-based 3D-pharmacophore model generation and virtual screening: identification of potential leads for P. falciparum DHFR enzyme inhibition
Chem. Biol. Drug Des.
75
115-126
2009
Plasmodium falciparum
Manually annotated by BRENDA team
Adane, L.; Bharatam, P.V.
Modelling and informatics in the analysis of P. falciparum DHFR enzyme inhibitors
Curr. Med. Chem.
15
1552-1569
2008
Plasmodium falciparum
Manually annotated by BRENDA team
Ojha, H.; Gahlot, P.; Tiwari, A.K.; Pathak, M.; Kakkar, R.
Quantitative Structure Activity Relationship Study of 2,4,6-Trisubstituted-s-triazine Derivatives as Antimalarial Inhibitors of Plasmodium Falciparum Dihydrofolate Reductase
Chem. Biol. Drug Des.
77
57-62
2011
Plasmodium falciparum
Manually annotated by BRENDA team
Carrasco, M.P.; Fotoran, W.L.; Cubillos, E.F.G.; Wunderlich, G.; Grotli, M.; Hollfelder, F.; Jackson, V.; King, R.D.; Oliver, S.G.
Plasmodium dihydrofolate reductase is a second enzyme target for the antimalarial action of triclosan
Sci. Rep.
8
1038
2018
Plasmodium falciparum, Plasmodium vivax
Manually annotated by BRENDA team