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10-formyl-dihydrofolate + NADPH + H+
10-formyl-tetrahydrofolate + NADP+
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
dihydrofolate + NADPH + H+
tetrahydrofolate + 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+
-
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
dihydrobiopterin + NADPH
? + NADP+
-
10% of the activity with 7,8-dihydrofolate
-
-
?
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
-
no 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
-
-
?
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 + 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
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+
-
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 + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
-
?
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
-
-
-
?
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
?
-
-
-
-
-
?
additional information
?
-
-
3-acetylpyridine adenine dinucleotide + dihydrofolate: rapid equilibrium random mechanism
-
-
?
additional information
?
-
-
NADPH + dihydrofolate: steady-state random mechanism
-
-
?
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(2,5-dimethyl-1,4-phenylene)bis(methylene) bis(N-[amino(imino)methyl](imidothiocarbamate))
50% inhibition at 0.000075 mM
(4-(1-[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(methyl)amino]ethyl)phenyl)methanol
-
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-(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
-
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
NSC80735, complete inhibition at 1 mM
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
1-[3-(aminomethyl)phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
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-((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
-
2-hydroxy-5-nitrobenzyl N-[amino(imino)methyl]imidothiocarbamate
50% inhibition at 0.0151 mM
2-methoxybenzyl N-[amino(imino)methyl]imidothiocarbamate
50% inhibition at 0.0033 mM
2-[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-8-yl]ethyl)amino]ethanol
-
2-[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(methyl)amino]-2-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-yl]ethanol
-
3,4-dichlorobenzyl N-[amino(imino)methyl]imidothiocarbamate
50% inhibition at 0.0037 mM
3,5-bis(trifluoromethyl)benzyl N-[amino(imino)methyl]imidothiocarbamate
50% inhibition at 0.0056 mM
3-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-(naphthalen-1-yl)ethyl)amino)propanoic acid
-
3-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)[1-(naphthalen-1-yl)ethyl]amino)propanoic acid
-
3-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1(2H)-yl)benzonitrile
-
3-(trifluoromethyl)benzyl N-[amino(imino)methyl]imidothiocarbamate
50% inhibition at 0.0043 mM
3-methoxybenzyl N-[amino(imino)methyl]imidothiocarbamate
50% inhibition at 0.0038 mM
4-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-(naphthalen-1-yl)ethyl)amino)butanoic acid
-
4-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)[1-(naphthalen-1-yl)ethyl]amino)butanoic acid
-
4-(trifluoromethyl)benzyl N-[amino(imino)methyl]imidothiocarbamate
50% inhibition at 0.013 mM
4-([(2,4-diaminopteridin-6-yl)methyl](methyl)amino)benzoic acid
-
4-methylbenzyl N-[amino(imino)methyl]imidothiocarbamate
50% inhibition at 0.0126 mM
4-[3-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1(2H)-yl)benzamido]benzene-1-sulfonyl fluoride
contains a fluorosulfonylphenylaminocarbonyl substitution at R2 on 1-phenyl-6,6-dimethyl-1,3,5-triazine-2,4-diamine ring, and shows the unique behavior of tight-binding and average inhibition, uncompetitive versus NADPH, competitive versus 7,8-dihydrofolate
4-[4,6-diamino-2-(4-chlorophenyl)-1,3,5-triazin-1(2H)-yl]benzene-1-sulfonamide
-
4-[4-[3-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1-yl)phenyl]butyl]benzenesulfonyl fluoride
uncompetitive versus NADPH, competitive versus 7,8-dihydrofolate
4-[6-[4-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1-yl)phenyl]hexyl]benzenesulfonyl fluoride
uncompetitive versus NADPH, competitive versus 7,8-dihydrofolate
6,6-dimethyl-1-(4-methylphenyl)-1,6-dihydro-1,3,5-triazine-2,4-diamine
-
6,6-dimethyl-1-[3-(4-phenylbutyl)phenyl]-1,6-dihydro-1,3,5-triazine-2,4-diamine
uncompetitive versus NADPH, competitive versus 7,8-dihydrofolate
6,7-bis(4-aminophenyl)pteridine-2,4-diamine
NSC61642
6-(([4-chlorotricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-yl]amino)methyl)pteridine-2,4-diamine
-
6-([(3-nitrophenyl)amino]methyl)pteridine-2,4-diamine
-
6-([(4-aminophenyl)amino]methyl)pteridine-2,4-diamine
-
6-([(4-ethoxyphenyl)amino]methyl)pteridine-2,4-diamine
-
6-([butyl(phenyl)amino]methyl)pteridine-2,4-diamine
-
6-([ethyl(phenyl)amino]methyl)pteridine-2,4-diamine
-
6-([methyl(3-nitrophenyl)amino]methyl)pteridine-2,4-diamine
-
6-([methyl(phenyl)amino]methyl)pteridine-2,4-diamine
-
6-([phenyl(prop-2-en-1-yl)amino]methyl)pteridine-2,4-diamine
-
6-([phenyl(propan-2-yl)amino]methyl)pteridine-2,4-diamine
-
6-([phenyl(propyl)amino]methyl)pteridine-2,4-diamine
-
6-([tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-ylamino]methyl)pteridine-2,4-diamine
-
6-([tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-8-ylamino]methyl)pteridine-2,4-diamine
-
6-[(phenylamino)methyl]pteridine-2,4-diamine
-
6-[(tricyclo[4.3.0.07,9]nona-1,3,5-trien-3-ylamino)methyl]pteridine-2,4-diamine
-
7-[(4-aminophenyl)methyl]-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine
NSC309401, AMPQD, a substrate analogue with the quinazoline-1, 3-diamine group, tight-binding inhibitor, complete inhibition at 1 mM, competitive inhibition of dihydrofolate binding. Potently inhibits the enzyme by competitive displacement of the substrate dihydrofolic acid, uncompetitive inhibition versus NADPH, the inhibitor has a markedly increased affinity for the NADPH-bound form of the enzyme. The mode of binding of the inhibitor to the enzyme-NADPH binary complex conforms to the slow-onset, tight-binding model
7H-pyrrolo(3,2-f)quinazoline-1,3-diamine
NSC339578
7H-pyrrolo[3,2-f]quinazoline-1,3-diamine
PQD, the lack of (4-aminophenyl)-methyl group at position 7 abolishes the slow-onset of inhibition
hydrochlorothiazide
sulfonamide diuretic, able to bind to DHFR
indapamide
sulfonamide diuretic, able to bind to DHFR
methyl 4-([(2,4-diaminopteridin-6-yl)methyl](methyl)amino)benzoate
-
methylbenzoprim
NSC382035
N-(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)-N-[1-(2-ethoxynaphthalen-1-yl)ethyl]-b-alanine
-
N7-(1-(naphthalen-1-yl)ethyl)-N7-propylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(2-aminoethyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(2-aminoethyl)-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(2-ethoxyethyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(2-ethoxyethyl)-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(2-propoxyethyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(2-propoxyethyl)-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(3-ethoxypropyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(3-ethoxypropyl)-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(4-aminobutyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(4-aminobutyl)-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(5-aminopentyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(5-aminopentyl)-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(cyclopropylmethyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(cyclopropylmethyl)-N7-[1-(4-methylnaphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(cyclopropylmethyl)-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(prop-2-en-1-yl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-(prop-2-en-1-yl)-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-benzyl-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-benzyl-N7-methylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-benzyl-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-butyl-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-butyl-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-cyclopropyl-N7-(1-(naphthalen-2-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-cyclopropyl-N7-[1-(naphthalen-2-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-ethyl-N7-(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-yl]ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-ethyl-N7-(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-8-yl]ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-ethyl-N7-(4-methylbenzyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-ethyl-N7-[1-(4-methylnaphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-methyl-N7-(1-phenylethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-methyl-N7-(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-yl]ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-methyl-N7-[1-(4-methylnaphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-methyl-N7-[1-(quinolin-4-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-methyl-N7-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-ylmethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-pentyl-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-pentyl-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[1-(1-benzothiophen-3-yl)ethyl]-N7-(cyclopropylmethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[1-(1-benzothiophen-3-yl)ethyl]-N7-ethylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[1-(1-benzothiophen-3-yl)ethyl]-N7-methylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[1-(2-ethoxynaphthalen-1-yl)ethyl]-N7-methylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[1-(2-ethylnaphthalen-1-yl)ethyl]-N7-methylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[1-(4-chloronaphthalen-1-yl)ethyl]-N7-(cyclopropylmethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[1-(naphthalen-1-yl)ethyl]-N7-propylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[2-(4-fluorophenyl)ethyl]-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[2-(4-fluorophenyl)ethyl]-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[2-(cyclohex-2-en-1-yl)ethyl]-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[2-(cyclohex-2-en-1-yl)ethyl]-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[3-(2-methyl-4H-imidazol-4-yl)propyl]-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[3-(2-methyl-4H-imidazol-4-yl)propyl]-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[3-(2-methylpropoxy)propyl]-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
N7-[3-(2-methylpropoxy)propyl]-N7-[1-(naphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
-
[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-8-yl]ethyl)amino]acetic acid
-
1,6-bis-(4-fluoro-phenyl)-[1,3,5]triazine-2,4-diamine
-
IC50: 0.011 nM, 0.03 mM 7,8-dihydrofolate
2,4-diaminopyrimidine
-
-
2-amino-4-oxo-6-methyl-5-phenylsulfanylthieno[2,3-d]pyrimidine
-
-
2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(2-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(3,4-dichlorophenyl)thio]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-ethylthieno[2,3-d ]-pyrimidin-4(3H)-one
-
-
2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(3,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-5-[(3-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-bromophenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-fluorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-(2-naphthylthio)thieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-(phenylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-fluorophenyl)sulfanyl]thieno[2,3-d ]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-methyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
3-heptyl-4-hydroxy-1H-naphthalen-2-one
-
IC50: 0.48 mM, 0.03 mM 7,8-dihydrofolate
5-(3,4,5-trimethoxy-benzyl)-pyrimidine-2,4-diamine
-
IC50: 18 nM, 0.03 mM 7,8-dihydrofolate
6,7-dimethyl-5,6,7,8-tetrahydro-quinazoline-2,4-diamine
-
IC50: 790 nM, 0.03 mM 7,8-dihydrofolate
6-(4-trifluoromethyl-phenoxy)-quinazoline-2,4-diamine
-
IC50: 660 nM, 0.03 mM 7,8-dihydrofolate
6-p-tolyloxy-quinazoline-2,4-diamine
-
IC50: 190 nM, 0.03 mM 7,8-dihydrofolate
6-p-tolylsulfanyl-quinazoline-2,4-diamine
-
IC50: 310 nM, 0.03 mM 7,8-dihydrofolate
7-methyl-5,6,7,8-tetrahydro-quinazoline-2,4-diamine
-
IC50: 0.011 nM, 0.03 mM 7,8-dihydrofolate
epigallocatechin gallate
-
bisubstrate inhibitor, binds both on substrate and cofactor site of dihydrofolate reductase. Detailed study on kinetics
N-(4-chloro-2-cyanophenyl)imidodicarbonimidic diamide
-
IC50: 320 nM, 0.03 mM 7,8-dihydrofolate
N-(4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d ]pyrimidin-5-yl)thio]benzoyl)-L-glutamic acid
-
-
N-(4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d ]pyrimidin-5-yl)thio]benzoyl)-L-glutamic acid
-
-
N-(4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl)-L-glutamic acid
-
binding mode, overview
organic mercurials
-
animal enzyme: activated, bacterial enzyme: unaffected or inhibited
-
peroxynitrite
-
0.1 mM, 50% inhibition of cysteine-free mutant C85S/C152E, no inhibition of wild-type
Urea
-
3 M, 15% inhibition
[amino-(4-[[(amino-thioureido-methyl)-amino]-methyl]-2,5-dimethyl-benzylamino)-methyl]-thiourea
-
IC50: 109 nM, 0.03 mM 7,8-dihydrofolate
methotrexate
50% inhibition at 0.000003 mM
methotrexate
enzyme-bound crystal structure analysis for inhibitor screening and docking studies, PDB ID 1RA3
methotrexate
-
-
methotrexate
-
dihydrofolate antagonist drug
additional information
inhibitory potencies of diverse 2,4-pteridinediamine derivates and pyrimido[4,5-d]pyrimidine-2,4-diamine derivates, molecular dynamic simulations, detailed overview
-
additional information
7H-pyrrolo(3,2-f) quinazoline-1, 3-diamine (PQD) inhibition kinetics, overview
-
additional information
analysis of 1,3,5-triazine-2,4-diamine and 1,2,4-triazine-2,4-diamine group-containing compounds as potential inhibitors of Escherichia coli DHFR. Fifteen derivatives of 1,3,5-triazine-2,4-diamine are assessed for their ability to bind to the apo form of enzyme EcDHFR. Quantitative structure-activity relationship analysis and macromolecular docking of the diaminotriazine series of compounds, overview. Effects of 1,3,5-triazine-2,4-diamine derivatives on the cofactor NADPH binding
-
additional information
-
analysis of 1,3,5-triazine-2,4-diamine and 1,2,4-triazine-2,4-diamine group-containing compounds as potential inhibitors of Escherichia coli DHFR. Fifteen derivatives of 1,3,5-triazine-2,4-diamine are assessed for their ability to bind to the apo form of enzyme EcDHFR. Quantitative structure-activity relationship analysis and macromolecular docking of the diaminotriazine series of compounds, overview. Effects of 1,3,5-triazine-2,4-diamine derivatives on the cofactor NADPH binding
-
additional information
-
overview
-
additional information
-
overview
-
additional information
-
overview: design of inhibitors from X-ray crystal structures
-
additional information
-
inhibitory effect increased with the radius of the cations
-
additional information
-
stereochemistry of inhibitor binding
-
additional information
-
stereochemistry of inhibitor binding
-
additional information
-
no inhibition with trimethoprim up to 1.38 mM
-
additional information
-
inhibitor synthesis and molecular modelling
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.003
10-formyl-dihydrofolate
pH 7.5, temperature not specified in the publication
0.0004 - 0.1161
7,8-dihydrofolate
0.00044 - 0.045
7,8-dihydrofolate
0.001
dihydrofolate
-
pH 7.0, 25°C, under atmospheric pressure
additional information
additional information
-
0.0004
7,8-dihydrofolate
chimera with Haemophilus influenzae enzyme, pH 7, 25°C
0.0007
7,8-dihydrofolate
chimera with Listeria grayi enzyme, pH 7, 25°C
0.0008
7,8-dihydrofolate
wild-type, pH 7, 25°C
0.0008
7,8-dihydrofolate
deletion mutant DELTAAla145, at pH 7.0 and 25°C
0.0012
7,8-dihydrofolate
mutant C85A/C152S, 15°C, pH 7.0
0.0012
7,8-dihydrofolate
mutant M1P/C85A/C152S, 15°C, pH 7.0
0.0012
7,8-dihydrofolate
wild-type, 15°C, pH 7.0
0.0012
7,8-dihydrofolate
-
wild-type, 15°C, pH 7.0
0.0013
7,8-dihydrofolate
mutant M1A/C85A/C152S, 15°C, pH 7.0
0.0013
7,8-dihydrofolate
wild type enzyme, at pH 7.0 and 25°C
0.0015
7,8-dihydrofolate
chimera with Saccharomyces cerevisiae enzyme, pH 7, 25°C
0.0025
7,8-dihydrofolate
mutant M1S/C85A/C152S, 15°C, pH 7.0
0.003
7,8-dihydrofolate
mutant M1A/M16F/M20L/M42Y/M92F/C85A/C152S, 15°C, pH 7.0
0.0038
7,8-dihydrofolate
mutant M1A/M16S/M20L/M42Y/M92F/C85A/C152S, 15°C, pH 7.0
0.0048
7,8-dihydrofolate
deletion mutant DELTAGly67/DELTAAla145, at pH 7.0 and 25°C
0.0051
7,8-dihydrofolate
deletion mutant DELTAGly67, at pH 7.0 and 25°C
0.0055
7,8-dihydrofolate
pH 7.5, temperature not specified in the publication
0.0056
7,8-dihydrofolate
deletion mutant DELTAGly67/DELTAGly121, at pH 7.0 and 25°C
0.0062
7,8-dihydrofolate
mutant linear ANLYF-G6, 15°C, pH 7.0
0.0063
7,8-dihydrofolate
chimera with Streptococcus dysgalactiae enzyme, pH 7, 25°C
0.0073
7,8-dihydrofolate
deletion mutant DELTAGly121/DELTAAla145, at pH 7.0 and 25°C
0.0083
7,8-dihydrofolate
mutant M1A/M16N/M20L/M42Y/M92F/C85A/C152S, 15°C, pH 7.0
0.0083
7,8-dihydrofolate
mutant M1A/M16N/M20L/M42Y/C85A/M92F/C152S, 15°C, pH 7.0
0.0086
7,8-dihydrofolate
mutant linear ANLYF-G8, 15°C, pH 7.0
0.0108
7,8-dihydrofolate
deletion mutant DELTAGly121, at pH 7.0 and 25°C
0.0115
7,8-dihydrofolate
mutant circular ANLYF-G6, 15°C, pH 7.0
0.013
7,8-dihydrofolate
mutant circular ANLYF-G7, 15°C, pH 7.0
0.014
7,8-dihydrofolate
mutant circular ANLYF-G8, 15°C, pH 7.0
0.0178
7,8-dihydrofolate
25°C, pH 7.0, pressure 0.1 MPa
0.0195
7,8-dihydrofolate
25°C, pH 7.0, pressure 200 MPa
0.0502
7,8-dihydrofolate
deletion mutant DELTAArg52/DELTAGly67, at pH 7.0 and 25°C
0.0512
7,8-dihydrofolate
deletion mutant DELTAArg52/DELTAGly121, at pH 7.0 and 25°C
0.058
7,8-dihydrofolate
chimera with Plasmodium falciparum enzyme, pH 7, 25°C
0.067
7,8-dihydrofolate
chimera with Homo sapiens enzyme, pH 7, 25°C
0.0777
7,8-dihydrofolate
deletion mutant DELTAArg52/DELTAAla145, at pH 7.0 and 25°C
0.1161
7,8-dihydrofolate
deletion mutant DELTAArg52, at pH 7.0 and 25°C
0.0046
NADPH
25°C, pH 7.0, pressure 200 MPa
0.0074
NADPH
pH 7.5, temperature not specified in the publication, cosubstrate: 10-formyl-dihydrofolate
0.008
NADPH
pH 7.5, temperature not specified in the publication, cosubstrate: 7,8-dihydrofolate
0.00044
7,8-dihydrofolate
-
-
0.00047
7,8-dihydrofolate
-
-
0.00061
7,8-dihydrofolate
-
mutant M42I, pH 7.0, 25°C
0.0007
7,8-dihydrofolate
-
mutant enzyme R44H, at 15°C, pH not specified in the publication
0.0007
7,8-dihydrofolate
-
pH 7, 20°C, wild-type enzyme
0.0008
7,8-dihydrofolate
-
mutant enzyme R44V, at 15°C, pH not specified in the publication
0.00082
7,8-dihydrofolate
-
mutant M42T, pH 7.0, 25°C
0.00083
7,8-dihydrofolate
-
mutant M42P, pH 7.0, 25°C
0.00091
7,8-dihydrofolate
-
mutant M42V, pH 7.0, 25°C
0.00097
7,8-dihydrofolate
-
wild-type enzyme from plasmid
0.001
7,8-dihydrofolate
-
mutant enzyme R44Y, at 15°C, pH not specified in the publication
0.0011
7,8-dihydrofolate
-
mutant enzyme R44C, at 15°C, pH not specified in the publication
0.00112
7,8-dihydrofolate
-
mutant M42L, pH 7.0, 25°C
0.00118
7,8-dihydrofolate
-
mutant M42G, pH 7.0, 25°C
0.00123
7,8-dihydrofolate
-
mutant L92M from plasmid
0.0013
7,8-dihydrofolate
-
wild-type, pH 7.0, 25°C
0.0013
7,8-dihydrofolate
-
mutant M42A, pH 7.0, 25°C
0.0014
7,8-dihydrofolate
-
mutant enzyme R44L, at 15°C, pH not specified in the publication
0.0015
7,8-dihydrofolate
-
mutant enzyme R44G, at 15°C, pH not specified in the publication
0.0016
7,8-dihydrofolate
-
mutant enzyme R44A, at 15°C, pH not specified in the publication
0.0016
7,8-dihydrofolate
-
wild type enzyme, at 15°C, pH not specified in the publication
0.00167
7,8-dihydrofolate
-
double mutant L16M/L20M from plasmid
0.00171
7,8-dihydrofolate
-
mutant L42M from plasmid
0.00178
7,8-dihydrofolate
-
mutant M42Y, pH 7.0, 25°C
0.0019
7,8-dihydrofolate
-
mutant enzyme R44E, at 15°C, pH not specified in the publication
0.00193
7,8-dihydrofolate
-
mutant M42H, pH 7.0, 25°C
0.00194
7,8-dihydrofolate
-
mutant M42C, pH 7.0, 25°C
0.0021
7,8-dihydrofolate
-
mutant enzyme R44I, at 15°C, pH not specified in the publication
0.00222
7,8-dihydrofolate
-
mutant L16M from plasmid
0.00227
7,8-dihydrofolate
-
mutant M42Q, pH 7.0, 25°C
0.00227
7,8-dihydrofolate
-
mutant M42S, pH 7.0, 25°C
0.0023
7,8-dihydrofolate
-
mutant enzyme R44M, at 15°C, pH not specified in the publication
0.0024
7,8-dihydrofolate
-
mutant enzyme R44Q, at 15°C, pH not specified in the publication
0.0025
7,8-dihydrofolate
-
mutant enzyme R44K, at 15°C, pH not specified in the publication
0.0025
7,8-dihydrofolate
-
mutant enzyme R44N, at 15°C, pH not specified in the publication
0.0025
7,8-dihydrofolate
-
mutant enzyme R44T, at 15°C, pH not specified in the publication
0.0027
7,8-dihydrofolate
-
mutant enzyme R44F, at 15°C, pH not specified in the publication
0.0027
7,8-dihydrofolate
-
pH 7, 20°C, monomeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli prepared by introducing residues located at the Thermotoga maritima dihydrofolate reductase dimer interface
0.00289
7,8-dihydrofolate
-
mutant L20M from plasmid
0.0029
7,8-dihydrofolate
-
mutant enzyme R44P, at 15°C, pH not specified in the publication
0.003
7,8-dihydrofolate
-
mutant enzyme R44D, at 15°C, pH not specified in the publication
0.0031
7,8-dihydrofolate
-
mutant enzyme R44S, at 15°C, pH not specified in the publication
0.00369
7,8-dihydrofolate
-
triple mutant L16M/L20M/L42M from plasmid
0.0037
7,8-dihydrofolate
-
mutant enzyme R44W, at 15°C, pH not specified in the publication
0.00597
7,8-dihydrofolate
-
mutant M42E, pH 7.0, 25°C
0.0077
7,8-dihydrofolate
-
pH 7, 20°C, dimeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli prepared by introducing residues located at the Thermotoga maritima dihydrofolate reductase dimer interface
0.0095
7,8-dihydrofolate
-
pH 6.0
0.0096
7,8-dihydrofolate
-
mutant isoform that carries the K32M mutation in gene copies 1 and 3 and the Q67H mutation in gene copies 2 and 4, pH 7.0, 30°C
0.014
7,8-dihydrofolate
-
mutant carrying the K32M mutation in gene copies 1 and 3 with the Q67H mutation in all gene copies, pH 7.0, 30°C
0.045
7,8-dihydrofolate
-
mutant M42W, pH 7.0, 25°C
0.268
NADH
-
-
0.0019
NADPH
-
pH 6.0
0.0019
NADPH
-
pH 7.0, 25°C, under atmospheric pressure
0.00228
NADPH
-
double mutant L16M/L20M from plasmid
0.00232
NADPH
-
mutant L16M from plasmid
0.0025 - 0.0032
NADPH
-
-
0.00252
NADPH
-
wild-type enzyme from plasmid
0.0027
NADPH
-
mutant L92M from plasmid
0.003
NADPH
-
mutant L42M from plasmid
0.0043
NADPH
-
mutant L20M from plasmid
0.00456
NADPH
-
triple mutant L16M/L20M/L42M from plasmid
0.0048
NADPH
-
pH 7, 20°C, wild-type enzyme
0.011
NADPH
-
mutant carrying the K32M mutation in gene copies 1 and 3 with the Q67H mutation in all gene copies, pH 7.0, 30°C
0.0195
NADPH
-
pH 7, 20°C, monomeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli prepared by introducing residues located at the Thermotoga maritima dihydrofolate reductase dimer interface
0.0199
NADPH
-
pH 7, 20°C, dimeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli prepared by introducing residues located at the Thermotoga maritima dihydrofolate reductase dimer interface
0.029
NADPH
-
mutant isoform that carries the K32M mutation in gene copies 1 and 3 and the Q67H mutation in gene copies 2 and 4, pH 7.0, 30°C
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
analysis of steady-state kinetics at pH 9.5
-
additional information
additional information
-
analysis of steady-state kinetics at pH 9.5
-
additional information
additional information
transient kinetics investigation of enzyme
-
additional information
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
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
additional information
molecular dynamics and spectroscopic analysis of the enzyme in transition state based on residues Tyr100 and Tyr111, overview
-
additional information
additional information
kinetic behavior of the wild-type enzyme ecDHFR and enzyme mutants D27S, Y100F, and D27S/Y100F across an extended pH range, including pH 9.0. Competitive hydrogen to deuterium and hydrogen to tritium kinetic isotope effects (KIEs) on the second-order rate constant (kcat/Km) are measured for wild-type and mutant ecDHFR variants to assess the intrinsic KIE on the catalyzed hydride transfer. Presteady-state, Michaelis-Menten, and single-turnover kinetics
-
additional information
additional information
-
kinetic behavior of the wild-type enzyme ecDHFR and enzyme mutants D27S, Y100F, and D27S/Y100F across an extended pH range, including pH 9.0. Competitive hydrogen to deuterium and hydrogen to tritium kinetic isotope effects (KIEs) on the second-order rate constant (kcat/Km) are measured for wild-type and mutant ecDHFR variants to assess the intrinsic KIE on the catalyzed hydride transfer. Presteady-state, Michaelis-Menten, and single-turnover kinetics
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
overview
-
additional information
additional information
-
overview
-
additional information
additional information
-
Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes
-
additional information
additional information
-
selenomethionine-containing mutants
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
4.6
10-formyl-dihydrofolate
pH 7.5, temperature not specified in the publication
0.22 - 96.3
7,8-dihydrofolate
0.05 - 104.6
7,8-dihydrofolate
2
acetylpyridine adenine nucleotide
-
with 7,8-dihydrofolate
18.4
dihydrofolate
-
pH 7.0, 25°C, under atmospheric pressure
additional information
additional information
-
0.22
7,8-dihydrofolate
deletion mutant DELTAGly121/DELTAAla145, at pH 7.0 and 25°C
0.37
7,8-dihydrofolate
deletion mutant DELTAArg52/DELTAGly121, at pH 7.0 and 25°C
0.38
7,8-dihydrofolate
deletion mutant DELTAGly67/DELTAGly121, at pH 7.0 and 25°C
1.7
7,8-dihydrofolate
deletion mutant DELTAGly121, at pH 7.0 and 25°C
4.6
7,8-dihydrofolate
mutant M1A/C85A/C152S, 15°C, pH 7.0
4.8
7,8-dihydrofolate
mutant M1P/C85A/C152S, 15°C, pH 7.0
4.9
7,8-dihydrofolate
mutant C85A/C152S, 15°C, pH 7.0
5.3
7,8-dihydrofolate
mutant M1S/C85A/C152S, 15°C, pH 7.0
5.3
7,8-dihydrofolate
wild-type, 15°C, pH 7.0
5.3
7,8-dihydrofolate
-
wild-type, 15°C, pH 7.0
9
7,8-dihydrofolate
chimera with Homo sapiens enzyme, pH 7, 25°C
10
7,8-dihydrofolate
chimera with Haemophilus influenzae enzyme, pH 7, 25°C
13
7,8-dihydrofolate
wild-type, pH 7, 25°C
14
7,8-dihydrofolate
chimera with Listeria grayi enzyme, pH 7, 25°C
16.2
7,8-dihydrofolate
mutant M1A/M16S/M20L/M42Y/M92F/C85A/C152S, 15°C, pH 7.0
16.5
7,8-dihydrofolate
deletion mutant DELTAGly67, at pH 7.0 and 25°C
22.8
7,8-dihydrofolate
pH 7.5, temperature not specified in the publication
23.1
7,8-dihydrofolate
deletion mutant DELTAArg52/DELTAGly67, at pH 7.0 and 25°C
24
7,8-dihydrofolate
deletion mutant DELTAAla145, at pH 7.0 and 25°C
24.8
7,8-dihydrofolate
wild type enzyme, at pH 7.0 and 25°C
25.8
7,8-dihydrofolate
mutant M1A/M16F/M20L/M42Y/M92F/C85A/C152S, 15°C, pH 7.0
29
7,8-dihydrofolate
chimera with Saccharomyces cerevisiae enzyme, pH 7, 25°C
31.9
7,8-dihydrofolate
deletion mutant DELTAArg52/DELTAAla145, at pH 7.0 and 25°C
33
7,8-dihydrofolate
chimera with Plasmodium falciparum enzyme, pH 7, 25°C
34.8
7,8-dihydrofolate
mutant circular ANLYF-G8, 15°C, pH 7.0
36.7
7,8-dihydrofolate
mutant linear ANLYF-G6, 15°C, pH 7.0
37
7,8-dihydrofolate
chimera with Streptococcus dysgalactiae enzyme, pH 7, 25°C
38.7
7,8-dihydrofolate
mutant circular ANLYF-G7, 15°C, pH 7.0
40.5
7,8-dihydrofolate
mutant M1A/M16N/M20L/M42Y/M92F/C85A/C152S, 15°C, pH 7.0
40.5
7,8-dihydrofolate
mutant M1A/M16N/M20L/M42Y/C85A/M92F/C152S, 15°C, pH 7.0
40.8
7,8-dihydrofolate
mutant linear ANLYF-G8, 15°C, pH 7.0
41.1
7,8-dihydrofolate
deletion mutant DELTAGly67/DELTAAla145, at pH 7.0 and 25°C
41.7
7,8-dihydrofolate
mutant linear ANLYF-G7, 15°C, pH 7.0
43.7
7,8-dihydrofolate
mutant circular ANLYF-G6, 15°C, pH 7.0
96.3
7,8-dihydrofolate
deletion mutant DELTAArg52, at pH 7.0 and 25°C
4.05
NADPH
pH 7.5, temperature not specified in the publication, cosubstrate: 10-formyl-dihydrofolate
28.1
NADPH
pH 7.5, temperature not specified in the publication, cosubstrate: 7,8-dihydrofolate
0.05
7,8-dihydrofolate
-
pH 7, 20°C, dimeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli prepared by introducing residues located at the Thermotoga maritima dihydrofolate reductase dimer interface
0.3
7,8-dihydrofolate
-
mutant enzyme R44P, at 15°C, pH not specified in the publication
0.49
7,8-dihydrofolate
-
mutant carrying the K32M mutation in gene copies 1 and 3 with the Q67H mutation in all gene copies, pH 7.0, 30°C
0.69
7,8-dihydrofolate
-
mutant enzyme R44D, at 15°C, pH not specified in the publication
0.89
7,8-dihydrofolate
-
mutant enzyme R44E, at 15°C, pH not specified in the publication
0.89
7,8-dihydrofolate
-
mutant enzyme R44Y, at 15°C, pH not specified in the publication
0.98
7,8-dihydrofolate
-
mutant enzyme R44L, at 15°C, pH not specified in the publication
1.15
7,8-dihydrofolate
-
mutant enzyme R44I, at 15°C, pH not specified in the publication
1.31
7,8-dihydrofolate
-
mutant enzyme R44V, at 15°C, pH not specified in the publication
1.39
7,8-dihydrofolate
-
mutant enzyme R44F, at 15°C, pH not specified in the publication
1.39
7,8-dihydrofolate
-
pH 7, 20°C, monomeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli prepared by introducing residues located at the Thermotoga maritima dihydrofolate reductase dimer interface
1.59
7,8-dihydrofolate
-
mutant enzyme R44H, at 15°C, pH not specified in the publication
1.7
7,8-dihydrofolate
-
mutant isoform that carries the K32M mutation in gene copies 1 and 3 and the Q67H mutation in gene copies 2 and 4, pH 7.0, 30°C
1.78
7,8-dihydrofolate
-
mutant enzyme R44G, at 15°C, pH not specified in the publication
1.9
7,8-dihydrofolate
-
mutant enzyme R44Q, at 15°C, pH not specified in the publication
2
7,8-dihydrofolate
-
with acetylpyridine adenine nucleotide
2
7,8-dihydrofolate
-
mutant enzyme R44T, at 15°C, pH not specified in the publication
2.41
7,8-dihydrofolate
-
mutant enzyme R44W, at 15°C, pH not specified in the publication
2.43
7,8-dihydrofolate
-
mutant enzyme R44C, at 15°C, pH not specified in the publication
3.05
7,8-dihydrofolate
-
mutant enzyme R44A, at 15°C, pH not specified in the publication
3.3
7,8-dihydrofolate
-
mutant enzyme R44N, at 15°C, pH not specified in the publication
3.8
7,8-dihydrofolate
-
mutant enzyme R44M, at 15°C, pH not specified in the publication
5.4
7,8-dihydrofolate
-
wild type enzyme, at 15°C, pH not specified in the publication
5.7
7,8-dihydrofolate
-
mutant enzyme R44K, at 15°C, pH not specified in the publication
5.8
7,8-dihydrofolate
-
mutant enzyme R44S, at 15°C, pH not specified in the publication
12.4
7,8-dihydrofolate
-
mutant M42I, pH 7.0, 25°C
12.6
7,8-dihydrofolate
-
pH 7, 20°C, wild-type enzyme
13
7,8-dihydrofolate
-
mutant M42G, pH 7.0, 25°C
13.7
7,8-dihydrofolate
-
wild-type enzyme from plasmid
14
7,8-dihydrofolate
-
mutant M42A, pH 7.0, 25°C
15.7
7,8-dihydrofolate
-
mutant M42V, pH 7.0, 25°C
15.9
7,8-dihydrofolate
-
mutant M42E, pH 7.0, 25°C
16.5
7,8-dihydrofolate
-
-
18
7,8-dihydrofolate
-
with NADPH
18.7
7,8-dihydrofolate
-
mutant M42T, pH 7.0, 25°C
18.9
7,8-dihydrofolate
-
mutant M42L, pH 7.0, 25°C
22.6
7,8-dihydrofolate
-
mutant M42S, pH 7.0, 25°C
24
7,8-dihydrofolate
-
mutant M42P, pH 7.0, 25°C
24.3
7,8-dihydrofolate
-
mutant M42Q, pH 7.0, 25°C
24.6
7,8-dihydrofolate
-
mutant L20M from plasmid
24.6
7,8-dihydrofolate
-
wild-type, pH 7.0, 25°C
25.2
7,8-dihydrofolate
-
double mutant L16M/L20M from plasmid
26.6
7,8-dihydrofolate
-
mutant M42H, pH 7.0, 25°C
30.4
7,8-dihydrofolate
-
mutant M42C, pH 7.0, 25°C
45.5
7,8-dihydrofolate
-
mutant M42Y, pH 7.0, 25°C
52.7
7,8-dihydrofolate
-
triple mutant L16M/L20M/L42M from plasmid
89
7,8-dihydrofolate
-
mutant M42W, pH 7.0, 25°C
104.6
7,8-dihydrofolate
-
mutant M42W, pH 7.0, 25°C
0.05
NADPH
-
pH 7, 20°C, dimeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli prepared by introducing residues located at the Thermotoga maritima dihydrofolate reductase dimer interface
1.39
NADPH
-
pH 7, 20°C, monomeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli prepared by introducing residues located at the Thermotoga maritima dihydrofolate reductase dimer interface
10
NADPH
-
per binding site
11
NADPH
-
with 7,8-dihydrofolate
12.6
NADPH
-
pH 7, 20°C, wild-type enzyme
19.2
NADPH
-
pH 7.0, 25°C, under atmospheric pressure
additional information
additional information
analysis of kinetic and thermodynamic fitting parameters and relaxation dispersion curves at different pH values and temperatures
-
additional information
additional information
-
analysis of kinetic and thermodynamic fitting parameters and relaxation dispersion curves at different pH values and temperatures
-
additional information
additional information
-
selenomethionine-containing mutants
-
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0.0068
(4-(1-[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(methyl)amino]ethyl)phenyl)methanol
Escherichia coli
pH 7.0, 37°C
0.019
1-(3-([(2,4-diaminopteridin-6-yl)methyl]amino)phenyl)ethanol
Escherichia coli
pH 7.0, 37°C
0.263
1-(3-ethoxyphenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
Escherichia coli
pH 7.3, 22°C
0.02091
1-(4-chlorophenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
Escherichia coli
pH 7.3, 22°C
0.0891
1-(4-ethoxyphenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
Escherichia coli
pH 7.3, 22°C
0.478
1-[3-(aminomethyl)phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
Escherichia coli
pH 7.3, 22°C
0.01845
1-[3-chloro-4-(5-phenylpentyl)phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
Escherichia coli
pH 7.3, 22°C
0.722
1-[4-(aminomethyl)phenyl]-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
Escherichia coli
pH 7.3, 22°C
0.0017
2-(2-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-(naphthalen-1-yl)ethyl)amino)ethoxy)ethanol
Escherichia coli
pH 7.0, 37°C
0.0003
2-[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-8-yl]ethyl)amino]ethanol
Escherichia coli
pH 7.0, 37°C
0.076
2-[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(methyl)amino]-2-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-yl]ethanol
Escherichia coli
pH 7.0, 37°C
0.00093
3-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-(naphthalen-1-yl)ethyl)amino)propanoic acid
Escherichia coli
pH 7.0, 37°C
0.02019
3-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1(2H)-yl)benzonitrile
Escherichia coli
pH 7.3, 22°C
0.00273
4-((5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-(naphthalen-1-yl)ethyl)amino)butanoic acid
Escherichia coli
pH 7.0, 37°C
0.0002
4-([(2,4-diaminopteridin-6-yl)methyl](methyl)amino)benzoic acid
Escherichia coli
pH 7.0, 37°C
0.06283
4-[3-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1(2H)-yl)benzamido]benzene-1-sulfonyl fluoride
Escherichia coli
pH 7.3, 22°C
1.548
4-[4,6-diamino-2-(4-chlorophenyl)-1,3,5-triazin-1(2H)-yl]benzene-1-sulfonamide
Escherichia coli
pH 7.3, 22°C
0.00115
4-[4-[3-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1-yl)phenyl]butyl]benzenesulfonyl fluoride
Escherichia coli
pH 7.3, 22°C
0.00184
4-[6-[4-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1-yl)phenyl]hexyl]benzenesulfonyl fluoride
Escherichia coli
pH 7.3, 22°C
0.03227
6,6-dimethyl-1-(4-methylphenyl)-1,6-dihydro-1,3,5-triazine-2,4-diamine
Escherichia coli
pH 7.3, 22°C
0.00759
6,6-dimethyl-1-[3-(4-phenylbutyl)phenyl]-1,6-dihydro-1,3,5-triazine-2,4-diamine
Escherichia coli
pH 7.3, 22°C
0.0006
6-(([4-chlorotricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-yl]amino)methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.1
6-([(4-aminophenyl)amino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.014
6-([(4-ethoxyphenyl)amino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.0006
6-([butyl(phenyl)amino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.00011
6-([ethyl(phenyl)amino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.00015
6-([phenyl(prop-2-en-1-yl)amino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.00088
6-([phenyl(propan-2-yl)amino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.00015
6-([phenyl(propyl)amino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.011
6-([tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-ylamino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.048
6-([tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-8-ylamino]methyl)pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.0022
6-[(phenylamino)methyl]pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.1
6-[(tricyclo[4.3.0.07,9]nona-1,3,5-trien-3-ylamino)methyl]pteridine-2,4-diamine
Escherichia coli
pH 7.0, 37°C
0.0022
methyl 4-([(2,4-diaminopteridin-6-yl)methyl](methyl)amino)benzoate
Escherichia coli
pH 7.0, 37°C
0.0083
N-(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)-N-[1-(2-ethoxynaphthalen-1-yl)ethyl]-b-alanine
Escherichia coli
pH 7.0, 37°C
0.00096
N7-(1-(naphthalen-1-yl)ethyl)-N7-propylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.002
N7-(2-aminoethyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.001
N7-(2-ethoxyethyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0033
N7-(2-propoxyethyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0035
N7-(3-ethoxypropyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0048
N7-(4-aminobutyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.003
N7-(5-aminopentyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0006
N7-(cyclopropylmethyl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0035
N7-(cyclopropylmethyl)-N7-[1-(4-methylnaphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0004
N7-(prop-2-en-1-yl)-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.00088
N7-benzyl-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0357
N7-benzyl-N7-methylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.00184
N7-butyl-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.004
N7-cyclopropyl-N7-(1-(naphthalen-2-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0002
N7-ethyl-N7-(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-yl]ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0032
N7-ethyl-N7-(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-8-yl]ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0214
N7-ethyl-N7-(4-methylbenzyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.00021
N7-ethyl-N7-[1-(4-methylnaphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0112
N7-methyl-N7-(1-phenylethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.000016
N7-methyl-N7-(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-yl]ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.000055
N7-methyl-N7-[1-(4-methylnaphthalen-1-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0007
N7-methyl-N7-[1-(quinolin-4-yl)ethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0035
N7-methyl-N7-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-7-ylmethyl]pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.00185
N7-pentyl-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.00027
N7-[1-(1-benzothiophen-3-yl)ethyl]-N7-(cyclopropylmethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.00015
N7-[1-(1-benzothiophen-3-yl)ethyl]-N7-ethylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.00005
N7-[1-(1-benzothiophen-3-yl)ethyl]-N7-methylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0011
N7-[1-(2-ethoxynaphthalen-1-yl)ethyl]-N7-methylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.003
N7-[1-(2-ethylnaphthalen-1-yl)ethyl]-N7-methylpyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0022
N7-[1-(4-chloronaphthalen-1-yl)ethyl]-N7-(cyclopropylmethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.00103
N7-[2-(4-fluorophenyl)ethyl]-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0025
N7-[2-(cyclohex-2-en-1-yl)ethyl]-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0008
N7-[3-(2-methyl-4H-imidazol-4-yl)propyl]-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.0034
N7-[3-(2-methylpropoxy)propyl]-N7-(1-(naphthalen-1-yl)ethyl)pyrimido[4,5-d]pyrimidine-2,4,7-triamine
Escherichia coli
pH 7.0, 37°C
0.021
[(5,7-diaminopyrimido[4,5-d]pyrimidin-2-yl)(1-[tricyclo[4.4.0.02,5]deca-1(10),2(5),6,8-tetraen-8-yl]ethyl)amino]acetic acid
Escherichia coli
pH 7.0, 37°C
0.000000011
1,6-bis-(4-fluoro-phenyl)-[1,3,5]triazine-2,4-diamine
Escherichia coli
-
IC50: 0.011 nM, 0.03 mM 7,8-dihydrofolate
0.035
2-amino-4-oxo-6-methyl-5-phenylsulfanylthieno[2,3-d]pyrimidine
Escherichia coli
-
-
0.000028
2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.028
2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
-
0.000033
2-amino-5-[(2-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.0028
2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
-
0.000022
2-amino-5-[(3,4-dichlorophenyl)thio]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.0000028
2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-ethylthieno[2,3-d ]-pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.0028
2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
-
0.000027
2-amino-5-[(3,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.000003
2-amino-5-[(3-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.000029
2-amino-5-[(4-bromophenyl)sulfanyl]-6-ethylthieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.000042
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.028
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
-
0.032
2-amino-5-[(4-fluorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
-
0.000028
2-amino-6-ethyl-5-(2-naphthylthio)thieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.000033
2-amino-6-ethyl-5-(phenylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.000033
2-amino-6-ethyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.000031
2-amino-6-ethyl-5-[(4-fluorophenyl)sulfanyl]thieno[2,3-d ]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.000039
2-amino-6-ethyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
pH 7.0, 37°C
0.058
2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
-
0.035
2-amino-6-methyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
-
0.0012
2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
Escherichia coli
-
-
0.48
3-heptyl-4-hydroxy-1H-naphthalen-2-one
Escherichia coli
-
IC50: 0.48 mM, 0.03 mM 7,8-dihydrofolate
0.000018
5-(3,4,5-trimethoxy-benzyl)-pyrimidine-2,4-diamine
Escherichia coli
-
IC50: 18 nM, 0.03 mM 7,8-dihydrofolate
0.00079
6,7-dimethyl-5,6,7,8-tetrahydro-quinazoline-2,4-diamine
Escherichia coli
-
IC50: 790 nM, 0.03 mM 7,8-dihydrofolate
0.00066
6-(4-trifluoromethyl-phenoxy)-quinazoline-2,4-diamine
Escherichia coli
-
IC50: 660 nM, 0.03 mM 7,8-dihydrofolate
0.00019
6-p-tolyloxy-quinazoline-2,4-diamine
Escherichia coli
-
IC50: 190 nM, 0.03 mM 7,8-dihydrofolate
0.00031
6-p-tolylsulfanyl-quinazoline-2,4-diamine
Escherichia coli
-
IC50: 310 nM, 0.03 mM 7,8-dihydrofolate
0.000000011
7-methyl-5,6,7,8-tetrahydro-quinazoline-2,4-diamine
Escherichia coli
-
IC50: 0.011 nM, 0.03 mM 7,8-dihydrofolate
0.0000000088 - 0.0000088
methotrexate
0.00032
N-(4-chloro-2-cyanophenyl)imidodicarbonimidic diamide
Escherichia coli
-
IC50: 320 nM, 0.03 mM 7,8-dihydrofolate
0.000001
N-(4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d ]pyrimidin-5-yl)thio]benzoyl)-L-glutamic acid
Escherichia coli
-
pH 7.0, 37°C
0.0000002
N-(4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d ]pyrimidin-5-yl)thio]benzoyl)-L-glutamic acid
Escherichia coli
-
pH 7.0, 37°C
0.0002
N-(4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl)-L-glutamic acid
Escherichia coli
-
-
0.00023
pemetrexed
Escherichia coli
-
pH 7.0, 37°C
0.23
permetrexed
Escherichia coli
-
-
0.00000001 - 0.00001
trimethoprim
0.000109
[amino-(4-[[(amino-thioureido-methyl)-amino]-methyl]-2,5-dimethyl-benzylamino)-methyl]-thiourea
Escherichia coli
-
IC50: 109 nM, 0.03 mM 7,8-dihydrofolate
0.0000000088
methotrexate
Escherichia coli
-
pH 7.0, 37°C
0.0000088
methotrexate
Escherichia coli
-
-
0.00000001
trimethoprim
Escherichia coli
-
pH 7.0, 37°C
0.00001
trimethoprim
Escherichia coli
-
-
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C85A/C152S
kinetic properties similar to wild-type
D27S
site-directed mutagenesis, the mutant shows a 3400fold reduced rate for the NADPH-dependent reduction of 7,8-dihydrofolate at pH 7.0 in water compared to wild-type
DELTAAla145
the mutant shows increased catalytic efficiency compared to the wild type enzyme
DELTAArg52
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
DELTAArg52/DELTAAla145
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
DELTAArg52/DELTAGly121
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
DELTAArg52/DELTAGly67
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
DELTAGly121
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
DELTAGly121/DELTAAla145
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
DELTAGly67
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
DELTAGly67/DELTAAla145
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
DELTAGly67/DELTAGly121
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
I14A
the mutant shows strongly reduced pre-steady-state rates of H transfer at 25°C and pH 7.0 compared to the wild type enzyme
I14G
the mutant shows severely reduced pre-steady-state rates of H transfer at 25°C and pH 7.0 compared to the wild type enzyme
I14V
the mutant shows reduced pre-steady-state rates of H transfer at 25°C and pH 7.0 compared to the wild type enzyme
L28F
mutant behaves similarly to wild-type
M1A/C85A/C152S
kinetic properties similar to wild-type
M1A/M16F/M20L/M42Y/M92F/C85A/C152S
hyperactive mutant, increase in dissociation rate constant of tetrahydrofolate from the enzyme-NADPH-tetrahydrofolate ternary complex
M1A/M16N/M20L/M42Y/C85A/M92F/C152S
mutant ANLYF carries seven amino acid substitutions that result in a methionine- and cysteine-free mutant enzyme with decreased stability. Mutant ANLYF show very high activity and may be stabilized by backbone cyclization via a cyanocysteine-mediated intramolecular ligation reaction, without loss of its high activity
M1A/M16N/M20L/M42Y/M92F/C85A/C152S
hyperactive mutant, increase in dissociation rate constant of tetrahydrofolate from the enzyme-NADPH-tetrahydrofolate ternary complex
M1A/M16S/M20L/M42Y/M92F/C85A/C152S
hyperactive mutant, increase in dissociation rate constant of tetrahydrofolate from the enzyme-NADPH-tetrahydrofolate ternary complex
M1P/C85A/C152S
kinetic properties similar to wild-type
M1S/C85A/C152S
kinetic properties similar to wild-type
Y100F
site-directed mutagenesis, the mutant shows a 14fold reduced rate for the NADPH-dependent reduction of 7,8-dihydrofolate at pH 7.0 in water compared to wild-type
Y100F/D27S
site-directed mutagenesis, the mutant shows an over 100000fold reduced rate for the NADPH-dependent reduction of 7,8-dihydrofolate at pH 7.0 in water compared to wild-type
C85S/C152E
-
cysteine-free mutant, analysis of inhibition by p.eroxynitrite. bicarbonate buffer protects mutant from inhibition by peroxynitrite. Decrease in mutant stability upon oxidation
I68M
compared to wild-type, low kcat/Km (DHF) values. Mutant allows growth in presence of sorbitol up to 1.44 osmol conditions
K32M
-
weakens binding of dihydrofolate over 60-fold, increases kcat value by a factor of 5
L16M
-
site-directed mutagenesis, same kinetic properties like the wild-type enzyme
L16M/L20M
-
site-directed mutagenesis, double mutant, elevated turnover number and specific activity
L16M/L20M/L42M
-
site-directed mutagenesis, triple mutant, elevated turnover number and specific activity
L16SeM
-
site-directed mutagenesis, with selenomethionine, same kinetic properties like the wild-type enzyme
L16SeM/L20SeM
-
site-directed mutagenesis, double mutant, with selenomethionine, elevated turnover number and specific activity
L16SeM/L20SeM/L42SeM
-
site-directed mutagenesis, triple mutant, with selenomethionine, elevated turnover number and specific activity
L20M
-
site-directed mutagenesis, elevated turnover number and specific activity
L20SeM
-
site-directed mutagenesis, with selenomethionine, elevated turnover number and specific activity
L42M
-
site-directed mutagenesis, same kinetic properties like the wild-type enzyme
L42SeM
-
site-directed mutagenesis, with selenomethionine, same kinetic properties like the wild-type enzyme
L54I
-
the mutation reduces the hydride transfer efficiency by about 100fold
L92M
-
site-directed mutagenesis, same kinetic properties like the wild-type enzyme
L92SeM
-
site-directed mutagenesis, with selenomethionine, same kinetic properties like the wild-type enzyme
M42A
-
45% decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42C
-
slight decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42E
-
6fold decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42G
-
45% decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42H
-
40% decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42I
-
slight increase in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42L
-
slight decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42P
-
50% increase in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42Q
-
45% decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42S
-
45% decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42T
-
slight increase in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42V
-
slight decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42W/G121V
-
kinetic isotope effect study, major change in the nature of H transfer, leading to poor reorganization and substantial gating
M42Y
-
30% increase in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
R44A
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44C
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44D
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44E
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44F
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44G
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44I
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44K
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44L
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44M
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44N
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44P
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44Q
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44S
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44T
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44V
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44W
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
R44Y
-
the mutation significantly reduces the enzymatic activity and the binding affinity toward the cofactor NADPH
Y69L
compared to wild-type, low kcat/Km (DHF) values. Mutant allows growth in presence of sorbitol up to 0.81 osmol conditions
G121V
reduced catalytic activity
G121V
the mutation interferes with coupled loop movements and appears to impair catalysis by destabilizing the closed Michaelis complex and introducing an extra step into the kinetic pathway
G121V
reduced catalytic efficiency due to significantly reduced pre-exponential factors, the chemical mechanism of catalysis is not impaired
G121V
-
kinetic isotope effect study, environmentally coupled tunnelling similar to wild-type
G121V
-
the mutation reduces the hydride transfer efficiency by about 100fold
M42W
-
6fold decrease in ratio kcat/Km, analysis of thermodynamic parameters for urea denaturation
M42W
-
kinetic isotope effect study, environmentally coupled tunnelling similar to wild-type
Q67H
-
about 100-fold tightening in binding to both dihydrolfolate and NADPH, mutation can help rescue the K32 M mutation
Q67H
mutant with reasonable catalytic efficiency, but displays substrate and cofactor inhibition. Contrary to wild-type which allows growth on all sorbitol conditions until the osmolyte concentration becomes too high or cell water content becomes too low, mutant Q67H allows growth up to 1.81 osmol conditions
additional information
double-labeling of enzyme with fluorescent quencher QSY35, at amino acid 17, and fluorescent probe Alexa555,at amino acid 35, by introducing Cys residues at these sites. Labeled enzyme retains full catalytic activity, analysis of first order rate constants for the stopped-flow fluorescent change of forward and reverse reaction
additional information
permutations in the N- and C-terminal domain show that for equilibrium and kinetic folding mechanism, a continuous adenosine-binding domain is required for a stable thermal intermediate and a continuous discontinuous loop domain is required for a stable urea intermediate
additional information
-
permutations in the N- and C-terminal domain show that for equilibrium and kinetic folding mechanism, a continuous adenosine-binding domain is required for a stable thermal intermediate and a continuous discontinuous loop domain is required for a stable urea intermediate
additional information
construction of mutants based on mutant M1A/M16N/M20L/M42Y/C85A/M92F/C152S, i.e. ANLYF. Linear ANLYF-Gn is ANLYF with the N- and C-terminal extensions of Ala-(Gly)n-3 and -(Gly)2-Cys-Ala residues, respectively, with n=6-8, and circular ANLYF-Gn is ANLYF with the C and N termini cross-linked by the linker of the -Gly-Gly-Ala-(Gly)n-3 sequence, n=6-8
additional information
-
construction of mutants based on mutant M1A/M16N/M20L/M42Y/C85A/M92F/C152S, i.e. ANLYF. Linear ANLYF-Gn is ANLYF with the N- and C-terminal extensions of Ala-(Gly)n-3 and -(Gly)2-Cys-Ala residues, respectively, with n=6-8, and circular ANLYF-Gn is ANLYF with the C and N termini cross-linked by the linker of the -Gly-Gly-Ala-(Gly)n-3 sequence, n=6-8
additional information
competitive hydrogen to deuterium and hydrogen to tritium kinetic isotope effects (KIEs) on the second-order rate constant (kcat/Km) are measured for wild-type and mutant ecDHFR variants to assess the intrinsic KIE on the catalyzed hydride transfer
additional information
-
competitive hydrogen to deuterium and hydrogen to tritium kinetic isotope effects (KIEs) on the second-order rate constant (kcat/Km) are measured for wild-type and mutant ecDHFR variants to assess the intrinsic KIE on the catalyzed hydride transfer
additional information
replacement of an integral alpha-helical segment of Escherichia coli DHFR with segments from a number of different organisms (Listeria grayi, Haemophilus influenzae, Streptococcus dysgalactiae, Saccharomyces cerevisiae, Plasmodium falciparum, Homo sapiens). The parameters most sensitive to helical replacement are KM and Ki. The rank orders of KM, Ki, change of Tm, and protein stability against unfolding to the molten-globule state are significantly correlated with helical content
additional information
-
replacement of an integral alpha-helical segment of Escherichia coli DHFR with segments from a number of different organisms (Listeria grayi, Haemophilus influenzae, Streptococcus dysgalactiae, Saccharomyces cerevisiae, Plasmodium falciparum, Homo sapiens). The parameters most sensitive to helical replacement are KM and Ki. The rank orders of KM, Ki, change of Tm, and protein stability against unfolding to the molten-globule state are significantly correlated with helical content
additional information
-
construction of a mutant isoform that carries the K32M mutation in gene copies 1 and 3 and the Q67H mutation in gene copies 2 and 4 of the tetrameric enzyme. Mutation Q67H can mostly compensate for mutation K32M. In a multimutant that combines the K32M mutation in gene copies 1 and 3 with the Q67H mutation in all gene copies, dihydrolflate is inhibitory, while NADPH is not. A mutant containing only the Q67H substitution in all four gene copies is severely inhibited by both NADPH and substrate
additional information
-
preparation of a dimeric variant (Xet-3) of dihydrofolate reductase from Escherichia coli by introducing residues located at the Thermotoga maritima dihydrofolate reductase (TmDHFR) dimer interface increases the melting temperature to about 60°C, approximately 9°C higher than that measured for the Escherichia coli enzyme. The steady-state and pre-steady-state rate constants measured for Xet-3 were similar to those of dimeric TmDHFR but significantly lower than those of the parent dihydrofolate reductase from Escherichia coli
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Dihydrofolate reductase
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Inhibitors of dihydrofolate reductase
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1988
Escherichia coli
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Escherichia coli
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Escherichia coli
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33
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Conformational changes in the active site loops of dihydrofolate reductase during the catalytic cycle
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2004
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High throughput screening identifies novel inhibitors of Escherichia coli dihydrofolate reductase that are competitive with dihydrofolate
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Escherichia coli
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Swanwick, R.S.; Maglia, G.; Tey, L.H.; Allemann, R.K.
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Escherichia coli (P0ABQ4), Escherichia coli
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Antikainen, N.M.; Smiley, R.D.; Benkovic, S.J.; Hammes, G.G.
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Biochemistry
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2005
Escherichia coli (P0ABQ4)
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Pu, J.; Ma, S.; Garcia-Viloca, M.; Gao, J.; Truhlar, D.G.; Kohen, A.
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Escherichia coli
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Ohmae, E.; Fukumizu, Y.; Iwakura, M.; Gekko, K.
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Escherichia coli
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Iwakura, M.; Maki, K.; Takahashi, H.; Takenawa, T.; Yokota, A.; Katayanagi, K.; Kamiyama, T.; Gekko, K.
Evolutional design of a hyperactive cysteine- and methionine-free mutant of Escherichia coli dihydrofolate reductase
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Escherichia coli (P0ABQ4), Escherichia coli
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Summerfield, R.L.; Daigle, D.M.; Mayer, S.; Mallik, D.; Hughes, D.W.; Jackson, S.G.; Sulek, M.; Organ, M.G.; Brown, E.D.; Junop, M.S.
A 2.13 A structure of E. coli dihydrofolate reductase bound to a novel competitive inhibitor reveals a new binding surface involving the M20 loop region
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Escherichia coli (P0ABQ4), Escherichia coli
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McElheny, D.; Schnell, J.R.; Lansing, J.C.; Dyson, H.J.; Wright, P.E.
Defining the role of active-site loop fluctuations in dihydrofolate reductase catalysis
Proc. Natl. Acad. Sci. USA
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2005
Escherichia coli (P0ABQ4)
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Wang, L.; Goodey, N.M.; Benkovic, S.J.; Kohen, A.
Coordinated effects of distal mutations on environmentally coupled tunneling in dihydrofolate reductase
Proc. Natl. Acad. Sci. USA
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Escherichia coli
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Svensson, A.K.; Zitzewitz, J.A.; Matthews, C.R.; Smith, V.F.
The relationship between chain connectivity and domain stability in the equilibrium and kinetic folding mechanisms of dihydrofolate reductase from E.coli
Protein Eng. Des. Sel.
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2006
Escherichia coli (P0ABQ4), Escherichia coli
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Boehr, D.D.; McElheny, D.; Dyson, H.J.; Wright, P.E.
The dynamic energy landscape of dihydrofolate reductase catalysis
Science
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Escherichia coli (P0ABQ4), Escherichia coli
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Krahn, J.M.; Jackson, M.R.; DeRose, E.F.; Howell, E.E.; London, R.E.
Crystal structure of a type II dihydrofolate reductase catalytic ternary complex
Biochemistry
46
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2007
Escherichia coli (P00383)
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Feng, J.; Goswami, S.; Howell, E.E.
R67, the other dihydrofolate reductase: rational design of an alternate active site configuration
Biochemistry
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555-565
2008
Escherichia coli
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Boehr, D.D.; Dyson, H.J.; Wright, P.E.
Conformational relaxation following hydride transfer plays a limiting role in dihydrofolate reductase catalysis
Biochemistry
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2008
Escherichia coli (P0ABQ4), Escherichia coli
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Ohmae, E.; Tatsuta, M.; Abe, F.; Kato, C.; Tanaka, N.; Kunugi, S.; Gekko, K.
Effects of pressure on enzyme function of Escherichia coli dihydrofolate reductase
Biochim. Biophys. Acta
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2008
Escherichia coli (P0ABQ4), Escherichia coli
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Meinhold, L.; Clement, D.; Tehei, M.; Daniel, R.; Finney, J.L.; Smith, J.C.
Protein dynamics and stability: the distribution of atomic fluctuations in thermophilic and mesophilic dihydrofolate reductase derived using elastic incoherent neutron scattering
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Geobacillus stearothermophilus, Escherichia coli (P0ABQ4)
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Thielges, M.C.; Case, D.A.; Romesberg, F.E.
Carbon-deuterium bonds as probes of dihydrofolate reductase
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Escherichia coli
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Takahashi, H.; Arai, M.; Takenawa, T.; Sota, H.; Xie, Q.H.; Iwakura, M.
Stabilization of hyperactive dihydrofolate reductase by cyanocysteine-mediated backbone cyclization
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Escherichia coli (P0ABQ4), Escherichia coli
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Chopra, S.; Dooling, R.M.; Horner, C.G.; Howell, E.E.
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Escherichia coli (P00383), Escherichia coli
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Lerner, M.G.; Bowman, A.L.; Carlson, H.A.
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Escherichia coli
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Arai, M.; Kondrashkina, E.; Kayatekin, C.; Matthews, C.R.; Iwakura, M.; Bilsel, O.
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Escherichia coli (P0ABQ4), Escherichia coli
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Escherichia coli (P0ABQ4), Escherichia coli
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Gloss, L.M.; Topping, T.B.; Binder, A.K.; Lohman, J.R.
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Divya, N.; Grifith, E.; Narayana, N.
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Escherichia coli (P00383)
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Khavrutskii, I.V.; Price, D.J.; Lee, J.; Brooks, C.L.
Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate
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Escherichia coli (P0ABQ4), Escherichia coli
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Spina, M.; Cuccioloni, M.; Mozzicafreddo, M.; Montecchia, F.; Pucciarelli, S.; Eleuteri, A.M.; Fioretti, E.; Angeletti, M.
Mechanism of inhibition of wt-dihydrofolate reductase from E. coli by tea epigallocatechin-gallate
Proteins
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2008
Escherichia coli
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Gangjee, A.; Qiu, Y.; Li, W.; Kisliuk, R.L.
Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d]pyrimidine antifolates
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Escherichia coli, Toxoplasma gondii, Homo sapiens (P00374), Homo sapiens
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Groff, D.; Thielges, M.C.; Cellitti, S.; Schultz, P.G.; Romesberg, F.E.
Efforts toward the direct experimental characterization of enzyme microenvironments: tyrosine100 in dihydrofolate reductase
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Escherichia coli (P0ABQ4)
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Banjanac, M.; Tatic, I.; Ivezic, Z.; Tomic, S.; Dumic, J.
Pyrimido-pyrimidines: A novel class of dihydrofolate reductase inhibitors
Food Technol. Biotechnol.
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Homo sapiens (P00374), Escherichia coli (P0ABQ4)
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Gangjee, A.; Li, W.; Kisliuk, R.L.; Cody, V.; Pace, J.; Piraino, J.; Makin, J.
Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents
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Escherichia coli, Toxoplasma gondii, Homo sapiens (P00374), Homo sapiens
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Batruch, I.; Javasky, E.; Brown, E.D.; Organ, M.G.; Johnson, P.E.
Thermodynamic and NMR analysis of inhibitor binding to dihydrofolate reductase
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Escherichia coli (P0ABQ4), Escherichia coli
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Murakami, C.; Ohmae, E.; Tate, S.; Gekko, K.; Nakasone, K.; Kato, C.
Cloning and characterization of dihydrofolate reductases from deep-sea bacteria
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Escherichia coli, Photobacterium profundum (D1MX70), Photobacterium profundum, Moritella yayanosii (D1MX71), Moritella yayanosii, Moritella japonica (D1MX72), Moritella japonica, Shewanella violacea (D1MYR1), Shewanella violacea
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Yokota, A.; Takahashi, H.; Takenawa, T.; Arai, M.
Probing the roles of conserved arginine-44 of Escherichia coli dihydrofolate reductase in its function and stability by systematic sequence perturbation analysis
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Escherichia coli
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Kamath, G.; Howell, E.; Agarwal, P.
The tail wagging the dog: Insights into catalysis in R67 dihydrofolate reductase
Biochemistry
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2010
Escherichia coli (P00383)
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Liu, C.T.; Wang, L.; Goodey, N.M.; Hanoian, P.; Benkovic, S.J.
Temporally overlapped but uncoupled motions in dihydrofolate reductase catalysis
Biochemistry
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2013
Escherichia coli
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Horiuchi, Y.; Ohmae, E.; Tate, S.; Gekko, K.
Coupling effects of distal loops on structural stability and enzymatic activity of Escherichia coli dihydrofolate reductase revealed by deletion mutants
Biochim. Biophys. Acta
1804
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2010
Escherichia coli (P0ABQ4), Escherichia coli
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Stojkovic, V.; Perissinotti, L.L.; Willmer, D.; Benkovic, S.J.; Kohen, A.
Effects of the donor-acceptor distance and dynamics on hydride tunneling in the dihydrofolate reductase catalyzed reaction
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Escherichia coli (P0ABQ4), Escherichia coli
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Srinivasan, B.; Tonddast-Navaei, S.; Skolnick, J.
Ligand binding studies, preliminary structure-activity relationship and detailed mechanistic characterization of 1-phenyl-6,6-dimethyl-1,3,5-triazine-2,4-diamine derivatives as inhibitors of Escherichia coli dihydrofolate reductase
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Escherichia coli (P0ABQ4), Escherichia coli
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Srinivasan, B.; Skolnick, J.
Insights into the slow-onset tight-binding inhibition of Escherichia coli dihydrofolate reductase detailed mechanistic characterization of pyrrolo [3,2-f] quinazoline-1,3-diamine and its derivatives as novel tight-binding inhibitors
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Escherichia coli (P0ABQ4)
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Liu, C.T.; Francis, K.; Layfield, J.P.; Huang, X.; Hammes-Schiffer, S.; Kohen, A.; Benkovic, S.J.
Escherichia coli dihydrofolate reductase catalyzed proton and hydride transfers temporal order and the roles of Asp27 and Tyr100
Proc. Natl. Acad. Sci. USA
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Escherichia coli (P0ABQ4), Escherichia coli
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Guo, J.; Loveridge, E.J.; Luk, L.Y.; Allemann, R.K.
Effect of dimerization on dihydrofolate reductase catalysis
Biochemistry
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2013
Escherichia coli, Thermotoga maritima (Q60034), Thermotoga maritima, Thermotoga maritima DSM 3109 (Q60034)
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Sah, S.; Shah, R.; Govindan, A.; Varada, R.; Rex, K.; Varshney, U.
Utilisation of 10-formyldihydrofolate as substrate by dihydrofolate reductase (DHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) tranformylase/IMP cyclohydrolase (PurH) in Escherichia coli
Microbiology
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982-991
2018
Escherichia coli (P0ABQ4), Escherichia coli, Escherichia coli K12 (P0ABQ4)
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Wan, Q.; Bennett, B.C.; Wymore, T.; Li, Z.; Wilson, M.A.; Brooks, C.L.; Langan, P.; Kovalevsky, A.; Dealwis, C.G.
Capturing the catalytic proton of dihydrofolate reductase Implications for general acid-Base catalysis
ACS Catal.
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5873-5884
2021
Escherichia coli (P0ABQ4), Escherichia coli
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Kaur, S.; Bhattacharyya, R.; Banerjee, D.
Hydrochlorothiazide and indapamide bind the NADPH binding site of bacterial dihydrofolate reductase results of an in-silico study and their implications
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Escherichia coli (P0ABQ4)
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Oyen, D.; Fenwick, R.B.; Aoto, P.C.; Stanfield, R.L.; Wilson, I.A.; Dyson, H.J.; Wright, P.E.
Defining the structural basis for allosteric product release from E. coli dihydrofolate reductase using NMR relaxation dispersion
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Escherichia coli (P0ABQ4), Escherichia coli
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Babu, C.S.; Lim, C.
Influence of solution ionic strength on the stabilities of M20 loop conformations in apo E. coli dihydrofolate reductase
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Escherichia coli (P0ABQ4), Escherichia coli
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Penhallurick, R.; Durnal, M.; Harold, A.; Ichiye, T.
Adaptations for pressure and temperature in dihydrofolate reductases
Microorganisms
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1706
2021
Escherichia coli, Moritella yayanosii
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Maffucci, I.; Laage, D.; Stirnemann, G.; Sterpone, F.
Differences in thermal structural changes and melting between mesophilic and thermophilic dihydrofolate reductase enzymes
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2020
Escherichia coli, Thermotoga maritima
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Kozlowski, R.; Zhao, J.; Dyer, R.B.
Acceleration of catalysis in dihydrofolate reductase by transient, site-specific photothermal excitation
Proc. Natl. Acad. Sci. USA
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Escherichia coli (P0ABQ4)
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Rodrigues, J.V.; Ogbunugafor, C.B.; Hartl, D.L.; Shakhnovich, E.I.
Chimeric dihydrofolate reductases display properties of modularity and biophysical diversity
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Escherichia coli (P0ABQ4), Escherichia coli
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