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10-formyl-dihydrofolate + NADPH + H+
10-formyl-tetrahydrofolate + NADP+
6-hydroxymethylpterin + NADPH
6-hydroxymethyl-7,8-dihydropterin + NADP+
-
-
-
-
?
6-methylpterin + NADPH
6-methyl-7,8-dihydropterin + NADP+
-
-
-
-
?
7,8-dihydrobiopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
7,8-dihydrofolate + acetylpyridine adenine nucleotide, reduced
5,6,7,8-tetrahydrofolate + acetylpyridine adenine nucleotide, oxidized
-
-
-
?
7,8-dihydrofolate + NADH + H+
5,6,7,8-tetrahydrofolate + NAD+
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
8-methylpterin + NADPH
8-methyl-7,8-dihydropterin + NADP+
biopterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
reaction of EC 1.5.1.33
-
-
?
D-erythro-7,8-neopterin + NADPH
?
-
low activity
-
-
?
D-threo-neopterin + NADPH
?
-
low activity
-
-
?
dihydrobiopterin + NADPH
? + NADP+
-
10% of the activity with 7,8-dihydrofolate
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
dihydropteroate + NADPH
?
-
-
-
-
?
dihydrosarcinapterin + NADPH + H+
tetrahydrosarcinapterin + NADP+
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
folate + NADPH + H+
7,8-dihydrofolate + NADP+
L-erythro-neopterin + NADPH
?
-
-
-
-
?
L-threo-7,8-dihydroneopterin + NADPH
?
-
low activity
-
-
?
L-threo-neopterin + NADPH
?
-
-
-
-
?
pterin + NADPH
7,8-dihydropterin + NADP+
-
low activity
-
-
?
xanthopterin + NADPH
?
-
low activity
-
-
?
additional information
?
-
10-formyl-dihydrofolate + NADPH + H+
10-formyl-tetrahydrofolate + NADP+
-
-
-
?
10-formyl-dihydrofolate + NADPH + H+
10-formyl-tetrahydrofolate + NADP+
the enzyme is involved in the folate recycling pathway
-
-
?
10-formyl-dihydrofolate + NADPH + H+
10-formyl-tetrahydrofolate + NADP+
-
-
-
?
10-formyl-dihydrofolate + NADPH + H+
10-formyl-tetrahydrofolate + NADP+
the enzyme is involved in the folate recycling pathway
-
-
?
7,8-dihydrobiopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
-
-
-
?
7,8-dihydrobiopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
-
-
-
?
7,8-dihydrobiopterin + NADPH + H+
5,6,7,8-tetrahydrobiopterin + NADP+
high activity, see also EC 1.5.1.33
-
-
?
7,8-dihydrofolate + NADH + H+
5,6,7,8-tetrahydrofolate + NAD+
-
-
-
-
r
7,8-dihydrofolate + NADH + H+
5,6,7,8-tetrahydrofolate + NAD+
-
-
-
-
r
7,8-dihydrofolate + NADH + H+
5,6,7,8-tetrahydrofolate + NAD+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
?, r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
directly correlated with thymidylate synthesis
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
key enzyme in biosynthesis of purines, pyrimidines and several amino acids
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
enzyme plays important role in nucleotide biosynthesis
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
reverse reaction at only one tenth of forward reaction
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
clear evidence against dihydrofolate substrate channeling in the bifunctional thymidylate synthase-dihydrofolate reductase
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
strongly specific for
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
ir
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
ir
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
?, r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
kinetic mechanism
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
cannot use NADH as reducing agent
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
water can serve as the Bronsted acid for the protonation of N5 of dihydrofolate during DHFR catalyzed reduction
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
Halalkalibacterium halodurans
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
Halalkalibacterium halodurans C-125
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
strongly specific for
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
enzyme content of methotrexate-insensitive cell line VA2-B is 200fold higher than that of sensitive cell line HeLa BU-25 due to production of alternate enzyme type
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
key role in thymidylate biosynthesis
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
ir
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
bifunctional enzyme DHFR-thymidylate synthase
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
?, r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
ir
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
ir
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
Pigeon
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
Pigeon
-
-
-
-
ir
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
DHFR activity is not essential for virus replication
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
protozoa
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
protozoa
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
ir
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
at neutral pH the forward reaction is favored
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium strongly favors tetrahydrofolate production
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
equilibrium constant: 320000000000
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
at pH 7 hydride transfer is at least partially rate limiting for temperatures below 50°C, at higher temperatures hydride transfer is faster than the steady state
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
DHFR catalyzes hydride transfer from the cofactor NADPH to 7,8-dihydrofolate to produce tetrahydrofolate requiring electrostatic complementarity between the enzyme and the transition state
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
the enzyme is involved in the folate recycling pathway
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
the enzyme is involved in the folate recycling pathway
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Halalkalibacterium halodurans
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Halalkalibacterium halodurans C-125
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
assay at 37°C
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
the reaction is essential in DNA synthesis
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
the conserved residues Leu28, Val31, Ile50 and Leu54 forming a hydrophobic pocket in the enzyme are the binding site for the p-aminobenzamide moiety of the substrate dihydrofolate
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Tequatrovirus T4
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
best substrate
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
8-methylpterin + NADPH
8-methyl-7,8-dihydropterin + NADP+
-
-
subsequently reduced more slowly and incompletely to 8-methyl-5,6,7,8-tetrahydropterin
?
8-methylpterin + NADPH
8-methyl-7,8-dihydropterin + NADP+
-
-
subsequently reduced more slowly and incompletely to 8-methyl-5,6,7,8-tetrahydropterin
?
8-methylpterin + NADPH
8-methyl-7,8-dihydropterin + NADP+
-
-
subsequently reduced more slowly and incompletely to 8-methyl-5,6,7,8-tetrahydropterin
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
r
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
no activity
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
no activity
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
no activity
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
no activity
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
no activity
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
slow rate
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
bifunctional enzyme DHFR-thymidylate synthase
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
at a slow rate, reaction not catalyzed by all dihydrofolate reductases
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
slow rate
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
no activity
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
no activity
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
slow rate
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
activity only at acidic pH around 4.5
-
?
folate + NADPH + H+
7,8-dihydrofolate + NADP+
-
-
-
?
folate + NADPH + H+
7,8-dihydrofolate + NADP+
-
-
-
?
additional information
?
-
a bifunctional enzyme with dihydrofolate reductase and thymidylate synthase activities, overview
-
-
?
additional information
?
-
-
a bifunctional enzyme with dihydrofolate reductase and thymidylate synthase activities, overview
-
-
?
additional information
?
-
-
equilibrium strongly favors tetrahydrofolate production
-
-
?
additional information
?
-
-
key enzyme in the biosynthesis of purines, pyrimidines and several amino acids
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
key enzyme in the biosynthesis of purines, pyrimidines and several amino acids
-
-
?
additional information
?
-
-
equilibrium strongly favors tetrahydrofolate production
-
-
?
additional information
?
-
-
no activity with 7,8-dihydrobiopterin and biopterin
-
-
?
additional information
?
-
-
no activity with folate, sepiapterin, isoxanthopterin, leucopterin
-
-
?
additional information
?
-
-
in Cryptosporidium, DHFR and thymidylate synthase are present as a bifunctional enzyme, DHFR-TS
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
3-acetylpyridine adenine dinucleotide + dihydrofolate: rapid equilibrium random mechanism
-
-
?
additional information
?
-
-
NADPH + dihydrofolate: steady-state random mechanism
-
-
?
additional information
?
-
enzyme activity decreases with increasing pressure. The Km values for dihydrofolate and NADPH are slightly higher at 200 MPa than at atmospheric pressure. The hydride transfer step is insensitive to pressure, while the dissociation constants of substrates and cofactors increase with pressure
-
-
?
additional information
?
-
-
enzyme activity decreases with increasing pressure. The Km values for dihydrofolate and NADPH are slightly higher at 200 MPa than at atmospheric pressure. The hydride transfer step is insensitive to pressure, while the dissociation constants of substrates and cofactors increase with pressure
-
-
?
additional information
?
-
free energy perturbation with molecular dynamics simulations of dihydrofolate reductase in complex with dihydrofolate. In the Michaelis complex the pKa is modulated by the Met20 loop fluctuations, providing the largest pKa shift in substrates with a tightly closed loop conformation, in the partially closed/open substrates, the pKa is similar to that in the occluded complex. Conducive to the protonation, tightly closing the Met20 loop enhances the interactions of the cofactor and the substrate with the Met20 side chain and aligns the nicotinamide ring of the cofactor coplanar with the pterin ring of the substrate
-
-
?
additional information
?
-
-
free energy perturbation with molecular dynamics simulations of dihydrofolate reductase in complex with dihydrofolate. In the Michaelis complex the pKa is modulated by the Met20 loop fluctuations, providing the largest pKa shift in substrates with a tightly closed loop conformation, in the partially closed/open substrates, the pKa is similar to that in the occluded complex. Conducive to the protonation, tightly closing the Met20 loop enhances the interactions of the cofactor and the substrate with the Met20 side chain and aligns the nicotinamide ring of the cofactor coplanar with the pterin ring of the substrate
-
-
?
additional information
?
-
-
equilibrium strongly favors tetrahydrofolate production
-
-
?
additional information
?
-
both dihydrolfolate reductase and thymidylate synthase are substrates for UBC9-catalyzed modification with small ubiquitin-like modifier-1
-
-
?
additional information
?
-
-
dihydrofolate reductase is a substrate of ubiquitin ligase MDM2. MDM2 binds directly to dihydrofolate reductase and catalyzes its monoubiquitination. It reduces dihydrofolate reductase activity in a p53-independent manner, but has no effect on the steady-state level of expression. the ability of MDM2 to inhibit dihydrofolate reductase deoends on an active MDM2 RING-finger domain
-
-
?
additional information
?
-
-
no activity with pterins
-
-
?
additional information
?
-
-
dihydrofolate reductase deficient mutant needs thymidine for growth, pathway overview
-
-
?
additional information
?
-
-
knockout mutants with either no pteridine reductase or dihydrofolate reductase activity revealed in comparison to wild-type that 90% of the cellular dihydrofolate reduction activity belongs to DHFR and 10% of the cellular dihydrofolate reductase activity belongs to pteridine reductase
-
-
?
additional information
?
-
-
assay method development
-
-
?
additional information
?
-
substrate binding site analysis, overview
-
-
?
additional information
?
-
-
substrate binding site analysis, overview
-
-
?
additional information
?
-
-
no activity with 7,8-dihydrobiopterin and biopterin
-
-
?
additional information
?
-
-
equilibrium strongly favors tetrahydrofolate production
-
-
?
additional information
?
-
molecular mechanism of the distinct differences in substrate channeling behavior between Toxoplasma gondii TS-DHFR and Cryptosporidium hominis TS-DHFR, overview
-
-
?
additional information
?
-
-
molecular mechanism of the distinct differences in substrate channeling behavior between Toxoplasma gondii TS-DHFR and Cryptosporidium hominis TS-DHFR, overview
-
-
?
additional information
?
-
the bifunctional folate and pyrimidine-metabolising enzyme dihydrofolate reductase-thymidylate synthase dihydrofolate reductase-thymidylate synthase is expressed from a single gene as a homodimer comprising of an N-terminal DHFR domain fused via a linker peptide to a thymidylate synthase domain at the C-terminus
-
-
?
additional information
?
-
-
the bifunctional folate and pyrimidine-metabolising enzyme dihydrofolate reductase-thymidylate synthase dihydrofolate reductase-thymidylate synthase is expressed from a single gene as a homodimer comprising of an N-terminal DHFR domain fused via a linker peptide to a thymidylate synthase domain at the C-terminus
-
-
?
additional information
?
-
no activity with folic acid and the structurally related pterins (biopterin, dihydrobiopterin, sepiapterin and neopterin) as substrates by enzyme DHFR-TS
-
-
?
additional information
?
-
-
no activity with folic acid and the structurally related pterins (biopterin, dihydrobiopterin, sepiapterin and neopterin) as substrates by enzyme DHFR-TS
-
-
?
additional information
?
-
the bifunctional folate and pyrimidine-metabolising enzyme dihydrofolate reductase-thymidylate synthase dihydrofolate reductase-thymidylate synthase is expressed from a single gene as a homodimer comprising of an N-terminal DHFR domain fused via a linker peptide to a thymidylate synthase domain at the C-terminus
-
-
?
additional information
?
-
no activity with folic acid and the structurally related pterins (biopterin, dihydrobiopterin, sepiapterin and neopterin) as substrates by enzyme DHFR-TS
-
-
?
additional information
?
-
although presumably not its primary physiological functions, this SDR pteridine reductase also exhibits dihydrofolate reductase (DHFR) activity in vitro. Substrate specificity, overview. No activity with biopterin and folate
-
-
-