Literature summary for 1.5.1.3 extracted from

Tahar, R.; de Pecoulas, P.E.; Basco, L.K.; Chiadmi, M.; Mazabraud, A.
Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli (2001), Mol. Biochem. Parasitol., 113, 241-249.

Search for more literature for 1.5.1.3

Application

Application	Comment	Organism
medicine	enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer	Plasmodium vivax

Cloned(Commentary)

Cloned (Comment)	Organism
DNA-sequence analysis	Plasmodium vivax
expression in Escherichia coli of wild-type and mutant enzymes	Plasmodium vivax

Protein Variants

Protein Variants	Comment	Organism
S58R/S117N	double mutant with naturally occurring point mutations, antifolate drug resistant	Plasmodium vivax

Inhibitors

Inhibitors	Comment	Organism	Structure
cycloguanil	wild-type and mutant	Plasmodium vivax
methotrexate	wild-type and mutant	Plasmodium vivax
pyrimethamine	wild-type and mutant	Plasmodium vivax
trimethoprim	wild-type and mutant	Plasmodium vivax

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
0.06	-	NADPH	wild-type enzyme	Plasmodium vivax
0.07	-	NADPH	mutant enzyme	Plasmodium vivax
0.097	-	7,8-dihydrofolate	mutant enzyme	Plasmodium vivax
0.107	-	7,8-dihydrofolate	wild-type enzyme	Plasmodium vivax

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
7,8-dihydrofolate + NADPH	Plasmodium vivax	DHFR activity is not essential for virus replication	5,6,7,8-tetrahydrofolate + NADP+	-	?

Organism

Organism	UniProt	Comment	Textmining
Plasmodium vivax	-	wild-type and mutant enzymes recombinant from Escherichia coli	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant from Escherichia coli	Plasmodium vivax

Renatured (Commentary)

Renatured (Comment)	Organism
wild-type and mutant, renaturation from inclusion bodies due to expression in E. coli, 200 mM KCl, 20 mM potassium phosphate, pH 7.0, 0.1 mM EDTA, 10 mM dithiothreitol	Plasmodium vivax

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
1.7	-	purified recombinant enzyme	Plasmodium vivax

Storage Stability

Storage Stability	Organism
-20°C, several months	Plasmodium vivax

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
7,8-dihydrofolate + NADPH	-	Plasmodium vivax	5,6,7,8-tetrahydrofolate + NADP+	-	?
7,8-dihydrofolate + NADPH	DHFR activity is not essential for virus replication	Plasmodium vivax	5,6,7,8-tetrahydrofolate + NADP+	-	?

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
25	-	assay at	Plasmodium vivax

Cofactor

Cofactor	Comment	Organism	Structure
NADPH	-	Plasmodium vivax

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.0000052	-	methotrexate	wild-type enzyme	Plasmodium vivax
0.0000069	-	methotrexate	mutant enzyme	Plasmodium vivax
0.000064	-	pyrimethamine	wild-type enzyme	Plasmodium vivax
0.000067	-	cycloguanil	wild-type enzyme	Plasmodium vivax
0.000098	-	trimethoprim	wild-type enzyme	Plasmodium vivax
0.000143	-	trimethoprim	mutant enzyme	Plasmodium vivax
0.000743	-	cycloguanil	mutant enzyme	Plasmodium vivax
0.00093	-	pyrimethamine	mutant enzyme	Plasmodium vivax

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Release 2023.1 (January 2023)