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Literature summary for 1.5.1.3 extracted from

  • Japrung, D.; Leartsakulpanich, U.; Chusacultanachai, S.; Yuthavong, Y.
    Conflicting requirements of Plasmodium falciparum dihydrofolate reductase mutations conferring resistance to pyrimethamine-WR99210 combination (2007), Antimicrob. Agents Chemother., 51, 4356-4360.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli Plasmodium falciparum

Protein Variants

Protein Variants Comment Organism
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 Plasmodium falciparum
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 Plasmodium falciparum
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 Plasmodium falciparum
N51I/C59R/S108N/I164L mutant highly resistant to pyrimethamine, but sensitive to WR99210, i.e. DHFT-QM mutant Plasmodium falciparum
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 Plasmodium falciparum
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 Plasmodium falciparum
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 Plasmodium falciparum

Inhibitors

Inhibitors Comment Organism Structure
pyrimethamine
-
Plasmodium falciparum
WR99210
-
Plasmodium falciparum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.005
-
7,8-dihydrofolate mutant N51I/C59R/N108T/I164L, pH 7.0 Plasmodium falciparum
0.0052
-
7,8-dihydrofolate mutant N51I/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
0.00595
-
NADPH mutant N51I/C59R/N108T/I164L, pH 7.0 Plasmodium falciparum
0.00643
-
NADPH mutant N51I/C59R/S108N/I164L, pH 7.0 Plasmodium falciparum
0.0065
-
NADPH mutant N51I/C59R/S108N/I164L/D187A, pH 7.0 Plasmodium falciparum
0.0072
-
NADPH mutant N51I/C59R/S108N/I164L/K96N, pH 7.0 Plasmodium falciparum
0.0081
-
7,8-dihydrofolate mutant N51I/C59R/S108N/I164L/K96N, pH 7.0 Plasmodium falciparum
0.0083
-
7,8-dihydrofolate mutant I51N/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
0.0113
-
NADPH mutant N51I/C59R/S108N/I164L/I150V/N182I/N201D, pH 7.0 Plasmodium falciparum
0.0133
-
7,8-dihydrofolate mutant N51I/C59R/S108N/I164L, pH 7.0 Plasmodium falciparum
0.0145
-
7,8-dihydrofolate mutant N51I/C59R/S108N/I164L/D187A, pH 7.0 Plasmodium falciparum
0.01465
-
7,8-dihydrofolate mutant N51I/C59R/S108N/I164L/I150V/N182I/N201D, pH 7.0 Plasmodium falciparum
0.0267
-
NADPH mutant I51N/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
0.052
-
NADPH mutant N51I/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
7,8-dihydrofolate + NADPH + H+
-
Plasmodium falciparum 5,6,7,8-tetrahydrofolate + NADP+
-
?

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.2
-
7,8-dihydrofolate mutant I51N/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
1.5
-
7,8-dihydrofolate mutant N51I/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
1.9
-
7,8-dihydrofolate mutant N51I/C59R/N108T/I164L, pH 7.0 Plasmodium falciparum
11.4
-
7,8-dihydrofolate mutant N51I/C59R/S108N/I164L/I150V/N182I/N201D, pH 7.0 Plasmodium falciparum
13.6
-
7,8-dihydrofolate mutant N51I/C59R/S108N/I164L/D187A, pH 7.0 Plasmodium falciparum
28.3
-
7,8-dihydrofolate mutant N51I/C59R/S108N/I164L/K96N, pH 7.0 Plasmodium falciparum
72
-
7,8-dihydrofolate mutant N51I/C59R/S108N/I164L, pH 7.0 Plasmodium falciparum

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00000085
-
WR99210 mutant N51I/C59R/S108N/I164L/K96N, pH 7.0 Plasmodium falciparum
0.0000011
-
WR99210 mutant N51I/C59R/S108N/I164L/I150V/N182I/N201D, pH 7.0 Plasmodium falciparum
0.0000012
-
WR99210 mutant N51I/C59R/S108N/I164L/D187A, pH 7.0 Plasmodium falciparum
0.0000021
-
WR99210 mutant N51I/C59R/S108N/I164L, pH 7.0 Plasmodium falciparum
0.0000036
-
WR99210 mutant I51N/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
0.0000073
-
WR99210 mutant N51I/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
0.0000081
-
pyrimethamine mutant I51N/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
0.0000155
-
WR99210 mutant N51I/C59R/N108T/I164L, pH 7.0 Plasmodium falciparum
0.0000176
-
pyrimethamine mutant N51I/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum
0.0000724
-
pyrimethamine mutant N51I/C59R/N108T/I164L, pH 7.0 Plasmodium falciparum
0.000147
-
pyrimethamine mutant N51I/C59R/S108N/I164L/I150V/N182I/N201D, pH 7.0 Plasmodium falciparum
0.000209
-
pyrimethamine mutant N51I/C59R/S108N/I164L, pH 7.0 Plasmodium falciparum
0.000292
-
pyrimethamine mutant N51I/C59R/S108N/I164L/K96N, pH 7.0 Plasmodium falciparum
0.000514
-
pyrimethamine mutant N51I/C59R/S108N/I164L/D187A, pH 7.0 Plasmodium falciparum

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00001
-
mutant N51I/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum pyrimethamine
0.00005
-
mutant N51I/C59R/S108N/I164L/D187A, pH 7.0 Plasmodium falciparum WR99210
0.00006
-
mutant N51I/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum WR99210
0.00009
-
mutant I51N/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum pyrimethamine
0.00009
-
mutant N51I/C59R/S108N/I164L/K96N, pH 7.0 Plasmodium falciparum WR99210
0.00016
-
mutant N51I/C59R/S108N/I164L, pH 7.0 Plasmodium falciparum WR99210
0.00017
-
mutant N51I/C59R/S108N/I164L, pH 7.0 Plasmodium falciparum pyrimethamine
0.0002
-
mutant I51N/C59R/N108S/I164L, pH 7.0 Plasmodium falciparum WR99210
0.00068
-
mutant N51I/C59R/N108T/I164L, pH 7.0 Plasmodium falciparum WR99210
0.00087
-
mutant N51I/C59R/S108N/I164L/D187A, pH 7.0 Plasmodium falciparum pyrimethamine
0.00092
-
mutant N51I/C59R/S108N/I164L/I150V/N182I/N201D, pH 7.0 Plasmodium falciparum WR99210
0.00182
-
mutant N51I/C59R/N108T/I164L, pH 7.0 Plasmodium falciparum pyrimethamine
0.00248
-
mutant N51I/C59R/S108N/I164L/K96N, pH 7.0 Plasmodium falciparum pyrimethamine
0.00347
-
mutant N51I/C59R/S108N/I164L/I150V/N182I/N201D, pH 7.0 Plasmodium falciparum pyrimethamine