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5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+

catalytic mechanism; rapid equilibrium random mechanism; substrate and cofactor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
catalytic mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
catalytic mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
catalytic mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
catalytic mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
catalytic mechanism
protozoa
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
catalytic mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
Pigeon
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
inhibitor binding mechanism
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
catalytic mechanism; cofactor binding mechanism, pH-dependence investigation
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
pteridine-binding site
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
kinetic mechanism; rapid random equilibrium mechanism with NADPH and reduced acetylpyridine adenine nucleotide as cofactor
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
bifunctional proteins with DHFR and thymidylate synthase activity
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
bifunctional proteins with DHFR and thymidylate synthase activity
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
bifunctional proteins with DHFR and thymidylate synthase activity
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
substrate and antifolate inhibitor methotrexate binding, modeling of three-dimensional structure
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
model for hydrogen transfer includes contributions from quantum mechanical tunnelling coupled with protein motions that actively modulate the tunnelling distance
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
ordered kinetic mechanism at elevated temperature around 60°C, with NADPH binding first. More random mechanism at temperatures around 20°C with greatly reduced Km-value for 7,8-dihydrofolate. Rate-limiting hydride-transfer with a moderate enthalpy of activiation
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
donor carbon at the hydride transfer transition state resembles the reactant state more than the product state, whereas the acceptor carbon is more productlike, a symptom of transition state imbalance
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
study on enzyme ternary complex with substrate analogue folates and oxidized NADP+ cofactor using NMR relaxation methods. Conformational exchanges of protein between a ground state with closed conformation of active site loops and an excited state with loops in occluded conformation. Fluctuations include motions of the nicotinamide ring of the cofactor into and out of the active site
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
kinetic isotope effect analysis, enzyme requires no no donor-acceptor distance fluctuations and thus no gating
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
analysis of higher energy conformational substates by NMR relaxation dispersion. The maximum hydride transfer and steady-state turnover rates are governed by the dynamics of transitions between ground and excited states of the intermediates. Model of conformational changes during the catalytic cycle
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
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+
the active-site loop dynamics access a closed conformation, and the accompanying closed to occluded rate constant is comparable to the maximum pH-independent hydride transfer rate constant. The closed to occluded conformational transition in the product ternary complex is a prerequisite for progression through the catalytic cycle. The rate of this process places an effective limit on the maximum rate of the hydride transfer step. The dynamics of the C-terminally associated region is pH-dependent, but the dynamics of the active-site loops and cofactor binding cleft are pH-independent
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
binding of NADPH is accompanied by release of 38 water molecules, while binding of dihydrofolate is accompanied by the net uptake of water
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
Ala16, Ile51, Cys59, Ser108 and Ile164 are active site residues
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
Ala16, Ile51, Cys59, Ser108 and Ile164 are active site residues, catalytic mechanism, overview
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
the product (tetrahydrofolate) dissociation step that is the rate-limiting step in Escherichia coli DHFR is significantly accelerated in spDHFR so that hydride transfer or a preceding step is rate-limiting
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
transfer of a proR hydride from the C4 atom of NADPH to the C6 position of the dihydropterin ring of DHF, mechanism of the proton and hydride transfer reaction, active site residues D27 and Y100 play a synergistic role in facilitating both the proton transfer and subsequent hydride transfer steps. Residue D27 appears to have a greater effect on the overall rate of conversion of DHF to tetrahydrofolate, Y100 plays an important electrostatic role in modulating the pKa of the N5 of DHF to enable the preprotonation of DHF by an active site water molecule. The D27 and Y100 residues function synergistically to provide an active site environment for the solvent-assisted protonation of N5 and to position the reacting substrates, NADPH and DHF, properly
-
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
-
-
-
-
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6-hydroxymethylpterin + NADPH
6-hydroxymethyl-7,8-dihydropterin + NADP+
-
-
-
-
?
6-methylpterin + NADPH
6-methyl-7,8-dihydropterin + 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 + NADP + H+
5,6,7,8-tetrahydrofolate + NADP+
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+
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
?
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + 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
?
-
7,8-dihydrofolate + NADP + H+

5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADP + H+
5,6,7,8-tetrahydrofolate + NADP+
-
assay at 37°C
-
-
?
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+
-
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+
-
-
-
-
?
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+
-
-
-
-
?
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+
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+
-
-
-
-
-
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+
Q70YQ6
-
-
-
?
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+
-
-
-
-
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+
-
-
-
?
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+
-
-
-
-
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+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
686360, 688381, 689962, 693567, 702667, 703158, 703803, 705018, 705800, 702275, 705044 -
-
?
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+
-
-
-
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+
-
the reaction is essential in DNA synthesis
-
-
?
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+
-
-
-
-
?
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+
Q2YY41
-
-
-
?
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+
-
-
-
-
?
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+
-
-
-
-
r
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+
-
-
-
-
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
-
?
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
?
-
-
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 substates with a tightly closed loop conformation, in the partially closed/open substates, 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
?
-
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
?
-
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
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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+
additional information
?
-
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+
-
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+
-
maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells
-
-
?
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+
-
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+
-
DHFR activity is not essential for virus replication
-
-
?
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 + H+

5,6,7,8-tetrahydrofolate + NADP+
B5U9U8
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
J7GQW2
-
-
-
?
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+
Q6FPH0
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Q27552
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Q834R2
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Q834R2
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
P00383
-
-
-
?
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+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Q86XF0
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Q7BPB0
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
A4H4P8
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
S5M3K7
-
-
-
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+
-
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+
Q9UUP5
-
-
-
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+
G4VJD6
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Q2YY41
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
P13955
-
-
-
?
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+
Q27783
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
Q27783
-
-
-
r
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
r
additional information

?
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key enzyme in the biosynthesis of purines, pyrimidines and several amino acids
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additional information
?
-
-
key enzyme in the biosynthesis of purines, pyrimidines and several amino acids
-
-
-
additional information
?
-
-
in Cryptosporidium, DHFR and thymidylate synthase are present as a bifunctional enzyme, DHFR-TS
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-
-
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
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-
-
additional information
?
-
Q27783
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
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-
-
additional information
?
-
Q27783
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
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(-)-epicatechin gallate
-
competitive to 7,8-dihydrofolate, formation of a slow dissociation ternary complex by the reaction of NADPH with the enzyme-inhibitor complex. Ionization state of E30 is critical for inhibitory activity
(-)-epigallocatechin gallate
-
competitive to 7,8-dihydrofolate, formation of a slow dissociation ternary complex by the reaction of NADPH with the enzyme-inhibitor complex. Ionization state of E30 is critical for inhibitory activity
(1E)-1-[4-[(3,5-dichloropyridin-4-yl)oxy]phenyl]ethanone thiosemicarbazone
-
-
(2,4-diaminopyrimidin-5-yl)methyl naphthalene-2-sulfonate
(2,5-dimethyl-1,4-phenylene)bis(methylene) bis(N-[amino(imino)methyl](imidothiocarbamate))
-
50% inhibition at 0.000075 mM
(2E)-1-(1-cyclohexylphthalazin-2(1H)-yl)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-(1-phenoxyphthalazin-2(1H)-yl)prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-(1-phenylphthalazin-2(1H)-yl)prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-(1-propylphthalazin-2(1H)-yl)prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(2-methylphenyl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(3,3,3-trifluoropropyl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(3,5-dimethylphenyl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(3-fluorophenyl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(3-methylbut-2-en-1-yl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(3-methylbutyl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(4-fluorophenyl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(4-methoxyphenoxy)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(4-methylphenoxy)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(4-methylphenyl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(hexan-3-yl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(propan-2-yl)phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-[4-(trifluoromethoxy)phenoxy]phthalazin-2(1H)-yl]prop-2-en-1-one
-
(2S)-2-((4-[(2-amino-6-ethyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)thio]benzoyl)amino)pentanedioic acid
-
50% inhibition at 0.00042 mM, additionally inhibitory on thymidylate synthase
(2S)-2-((4-[(2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)thio]benzoyl)amino)pentanedioic acid
-
50% inhibition at 0.0021 mM, additionally inhibitory on thymidylate synthase
(2S)-2-[(4-([(2,4-diaminopteridin-6-yl)methyl](methyl)amino)phenyl)formamido]pentanedioic acid
-
i.e, methotrexate, A DHFR inhibitor, binds at the DHFR active site
-
(2S)-2-[(5-{methyl[(2-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl]amino}thiophen-2-yl)formamido]pentanedioic acid
-
in low-folate medium, up to 300-fold increase of inhibitory activity
(4-(1-[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(methyl)amino]ethyl)phenyl)methanol
(E)-5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamine
(Z)-5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamine
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
1,3-phenylenebis(methylene) bis(N-[amino(imino)methyl](imidothiocarbamate))
-
50% inhibition at 0.000075 mM
1,4-bis-([N-(1-imino-1-guanidino-methyl)]sulfanylmethyl)-3,6-dimethyl-benzene
-
binding of the inhibitor has both a favorable entropy and enthalpy of binding. Positive binding cooperativity between inhibitor and the cofactor NADPH. Binding of inhibitor to DHFR is 285fold tighter in the presence of the NADPH cofactor than in its absence
1,4-phenylenebis(methylene) bis(N-[amino(imino)methyl](imidothiocarbamate))
-
-
1,6-bis-(4-fluoro-phenyl)-[1,3,5]triazine-2,4-diamine
-
IC50: 0.011 nM, 0.03 mM 7,8-dihydrofolate
1-(3-([(2,4-diaminopteridin-6-yl)methyl]amino)phenyl)ethanol
1-(3-ethoxyphenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
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-
1-(4-chlorophenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
1-(4-ethoxyphenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
-
1-(4-nitrophenyl)-3-[4-[4-[(4-nitrophenyl)carbamoylamino]phenoxy]phenyl]urea
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NSC80735, complete inhibition at 1 mM
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1-([N-(1-imino-guanidino-methyl)]sulfanylmethyl)-3-trifluoromethyl-benzene
-
binding of the inhibitor has both a favorable entropy and enthalpy of binding. Positive binding cooperativity between inhibitor and the cofactor NADPH. Binding of inhibitor to DHFR in the absence of NADPH is not observed
1-N,4-N-bis(4-aminophenyl)benzene-1,4-dicarboxamide
-
NSC55152, complete inhibition at 1 mM
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1-[3-(3,4-dichlorophenoxy)propyloxy]-5-isopropylbiguanide
-
i.e. PS-16
1-[3-(4-chlorophenoxy)propyloxy]-5-isopropylbiguanide
-
i.e. PS-33
1-[3-(aminomethyl)phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
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1-[3-chloro-4-(5-phenylpentyl)phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
uncompetitive versus NADPH, competitive versus 7,8-dihydrofolate
1-[4-(aminomethyl)phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
-
1-[4-(dimethylamino)phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
-
1-[4-[4-(2,4-dichlorophenyl)butyl]phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
-
11H-benzo[b][1]benzazepine
-
NSC123458, 87% inhibition at 1 mM
-
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
-
-
2,4,6-Trinitrobenzenesulfonic acid
-
-
2,4-diamino-5,6-dihydro-6,6-dimethyl-5-(4'-methoxyphenyl)-s-triazine
-
-
2,4-diamino-5-((R)-3-(3,4,5-trimethoxyphenyl)but-1-ynyl)-6-methylpyrimidine
2,4-diamino-5-((S)-3-(3,4,5-trimethoxyphenyl)but-1-ynyl)-6-methylpyrimidine
2,4-diamino-5-(3-(2,5-dimethoxyphenyl)prop-1-ynyl)-6-ethylpyrimidine
-
i.e. UCP120B, potent enzyme inhibitor of DHFR and bacterial growth, three-dimensional solution structure of the ternary complex with enzyme and NADPH cofactor determined by NMR from 20 mM TES, 50 mM KCl, 10 mM DTT, and 0.5 mM EDTA solution containing 2 mM of each ligand, comparison to the crystal structure of the ternary complex, overview. Analysis of structure and dynamics of the binary inhibitor-enzyme complex
2,4-diamino-5-(3-(3,4,5-trimethoxyphenyl)but-1-ynyl)-6-methylpyrimidine
2,4-diamino-5-(3-(3,4,5-trimethoxyphenyl)but-1-ynyl)pyrimidine
2,4-diamino-5-(3-(3,4,5-trimethoxyphenyl)prop-1-ynyl)-6-methylpyrimidine
2,4-diamino-5-(3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-ynyl)-6-methylpyrimidine
2,4-diamino-5-(3-phenylprop-1-ynyl)-6-ethylpyrimidine
2,4-Diamino-5-adamantylpyrimidine
2,4-Diamino-5-benzylpyrimidines
-
-
2,4-diamino-5-isopropyl-6-(phenylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidine
-
-
2,4-diamino-5-isopropyl-6-arylthio-7H-pyrrolo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(1-naphthylthio)furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(2',3',5',6'-tetrafluoro-4'-trifluoromethylphenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(2',5'-dimethoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(2',6'-dichlorophenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(2',6'-dimethylphenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(2'-isopropyl-6'-methylphenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(2'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(2-naphthylthio)furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(3',4'-dimethoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(3'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-6-(4'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
2,4-diamino-5-methyl-butylpyrido[2,3-d]pyrimidine
-
-
2,4-Diamino-5-phenyl-s-triazines
-
-
2,4-diamino-5-propyl-6-(1'-naphthylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidine
-
-
2,4-diamino-5-propyl-6-arylthio-7H-pyrrolo[2,3-d]pyrimidine
2,4-diamino-5-[(R)-3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
-
-
2,4-diamino-5-[(S)-3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
-
-
2,4-diamino-5-[3-(2,3-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-npropylpyrimidine
2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]pyrimidine
2,4-diamino-5-[3-(2-methoxy-5-phenylphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
-
2,4-diamino-5-[3-(2-phenyl-5-methoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
-
2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)-3-methylbut-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)pent-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
2,4-diamino-5-[3-(3-methoxy-4-(2,6-diisopropylphenyl)phenyl)-but-1-ynyl]-6-methylpyrimidine
-
-
2,4-diamino-5-[3-(3-methoxy-4-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
-
2,4-diamino-5-[3-(3-methoxy-4-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
-
2,4-diamino-5-[3-(3-methoxy-4-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
-
-
2,4-diamino-5-[3-(3-methoxy-5-(2,6-diisopropylphenyl)phenyl)-but-1-ynyl]-6-methylpyrimidine
-
-
2,4-diamino-5-[3-(3-methoxy-5-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(3-methoxy-5-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(3-methoxy-5-(3,5-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(3-methoxy-5-(4-methoxyphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(3-methoxy-5-(4-tertbutylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(3-methoxy-5-(6-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
2,4-diamino-5-[3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
-
-
2,4-diamino-6-(2-hydroxydibenz[b,f]azepin-5-yl)methylpteridine
-
crystallization data
2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine
-
2,4-diamino-6-[(3',4',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine
-
2,4-diamino-6-[N-(2,3,5-trichlorobenzyl)-N-ethylamino]quinazoline
2,4-diamino-6-[N-(2,5-dimethoxybenzyl)-N-cyclopropyl methylamino]quinazoline
2,4-diamino-6-[N-(2,5-dimethoxybenzyl)-N-ethylamino]quinazoline
2,4-diamino-6-[N-(2,5-dimethoxybenzyl)-N-propylamino]quinazoline
2,4-diamino-6-[N-(alpha-naphthyl)-N-ethylamino]quinazoline
2,4-diamino-6-[N-(benzyl)-N-ethylamino]quinazoline
2,4-diamino-6-[N-(beta-naphthyl)-N-cyclopropyl methylamino]-quinazoline
2,4-diamino-6-[N-(beta-naphthyl)-N-ethylamino]quinazoline
2,4-diamino-6-[N-(beta-naphthyl)-N-propylamino]quinazoline
2,4-Dimamino-6-butylpyrido[2,3-d]pyrimidine
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2-(2-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-(naphthalen-1-yl)ethyl)amino)ethoxy)ethanol
2-(2-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)[1-(naphthalen-1-yl)ethyl]amino)ethoxy)ethanol
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2-(3-(2-(hydroxyimino)-2-(pyridine-4-yl)-6,7-dimethylquinoxalin-2-yl)-1-(pyridine-4-yl)ethanone) oxime
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