PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
17916364-1	2007	Escherichia coli dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate.	dihydrofolate	17-30	Dihydrofolate reductase	Escherichia coli	42-46
18724364-5	2008	Instead, it arises from accumulation of DHFR"s substrate dihydrofolate, which we show is a potent FP-gamma-GS inhibitor.	dihydrofolate	57-70	Dihydrofolate reductase	Escherichia coli	40-44
18804698-1	2008	Dihydrofolate reductase (DHFR) enzyme catalyzes tetrahydrofolate regeneration by reduction of dihydrofolate using NADPH as a cofactor.	dihydrofolate	94-107	dihydrofolate reductase	Homo sapiens	0-23
18804698-1	2008	Dihydrofolate reductase (DHFR) enzyme catalyzes tetrahydrofolate regeneration by reduction of dihydrofolate using NADPH as a cofactor.	dihydrofolate	94-107	dihydrofolate reductase	Homo sapiens	25-29
18247058-3	2008	Dihydrofolate reductase catalyzes the reduction of folic acid to dihydrofolate and thereafter to tetrahydrofolate.	dihydrofolate	65-78	dihydrofolate reductase	Homo sapiens	0-23
18056255-1	2008	Dihydrofolate reductase (DHFR) catalyzes folic acid reduction and recycles dihydrofolate generated during dTMP biosynthesis to tetrahydrofolate.	dihydrofolate	75-88	dihydrofolate reductase	Danio rerio	0-23
18056255-1	2008	Dihydrofolate reductase (DHFR) catalyzes folic acid reduction and recycles dihydrofolate generated during dTMP biosynthesis to tetrahydrofolate.	dihydrofolate	75-88	dihydrofolate reductase	Danio rerio	25-29
18056255-9	2008	In addition, the DHFR-mediated dihydrofolate reduction was significantly inhibited by its own substrate folic acid.	dihydrofolate	31-44	dihydrofolate reductase	Danio rerio	17-21
18086667-1	2008	R67 dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate using NADPH as a cofactor.	dihydrofolate	4-17	dihydrofolate reductase	Escherichia coli	29-33
16790925-1	2006	R67 plasmid-encoded dihydrofolate reductase (R67 DHFR) is an NADPH-dependent homotetrameric enzyme that catalyzes the reduction of dihydrofolate to tetrahydrofolate.	dihydrofolate	20-33	dihydrofolate reductase	Homo sapiens	49-53
17413111-1	2007	BACKGROUND: Dihydrofolate reductase (DHFR) converts dihydrofolate (DHF) into tetrahydrofolate (THF) and plays an essential role in cell metabolism and cellular growth.	dihydrofolate	52-65	dihydrofolate reductase	Homo sapiens	12-35
17413111-1	2007	BACKGROUND: Dihydrofolate reductase (DHFR) converts dihydrofolate (DHF) into tetrahydrofolate (THF) and plays an essential role in cell metabolism and cellular growth.	dihydrofolate	52-65	dihydrofolate reductase	Homo sapiens	37-41
17413111-1	2007	BACKGROUND: Dihydrofolate reductase (DHFR) converts dihydrofolate (DHF) into tetrahydrofolate (THF) and plays an essential role in cell metabolism and cellular growth.	dihydrofolate	37-40	dihydrofolate reductase	Homo sapiens	12-35
17346178-4	2007	DHFR catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), an essential cofactor in the biosynthesis of thymidylate monophosphate (dTMP).	dihydrofolate	32-45	dihydrofolate reductase	Homo sapiens	0-4
26443588-2	2007	All the folic acid derivatives that serve as recipients and donors of one-carbon units are derivatives of tetrahydrofolate, which is formed from dihydrofolate by an NADPH-dependent reduction catalyzed by dihydrofolate reductase (FolA).	dihydrofolate	145-158	dihydrofolate reductase type I	Escherichia coli	229-233
16969375-2	2007	The gene dihydrofolate reductase (DHFR) is primarily involved in the reduction of dihydrofolate, generated during thymidylate synthesis, to tetrahydrofolate in order to maintain adequate amounts of folate for DNA synthesis and homocysteine remethylation.	dihydrofolate	9-22	dihydrofolate reductase	Homo sapiens	34-38
16873119-1	2006	Dihydrofolate reductase (DHFR) maintains the intracellular pool of tetrahydrofolate through catalysis of hydrogen transfer from reduced nicotinamide adenine dinucleotide to 7,8-dihydrofolate.	dihydrofolate	173-190	dihydrofolate reductase	Escherichia coli	25-29
15726569-3	2005	Using the semiempirical PM3 method to model the QM region, the application of this PQA/MM method is illustrated by calculation of the relative protonation free energy of the conserved OD2 (Asp27) and the N5 (dihydrofolate) proton acceptor sites in the active site of Escherichia coli dihydrofolate reductase (DHFR) with the bound nicotinamide adenine dinucleotide phosphate (NADPH) cofactor.	dihydrofolate	208-221	Dihydrofolate reductase	Escherichia coli	284-307
16241906-1	2006	The enzyme DHFR (dihydrofolate reductase) catalyses hydride transfer from NADPH to, and protonation of, dihydrofolate.	dihydrofolate	17-30	Dihydrofolate reductase	Escherichia coli	11-15
15858267-3	2005	Despite exhaustive investigation of the catalytic mechanism of DHFR, controversy persists over the exact pathway associated with proton donation in reduction of the substrate, dihydrofolate.	dihydrofolate	176-189	dihydrofolate reductase	Escherichia coli	63-67
15726569-3	2005	Using the semiempirical PM3 method to model the QM region, the application of this PQA/MM method is illustrated by calculation of the relative protonation free energy of the conserved OD2 (Asp27) and the N5 (dihydrofolate) proton acceptor sites in the active site of Escherichia coli dihydrofolate reductase (DHFR) with the bound nicotinamide adenine dinucleotide phosphate (NADPH) cofactor.	dihydrofolate	208-221	Dihydrofolate reductase	Escherichia coli	309-313
16003948-10	2005	Dihydrofolic acid (DHF) was a much poorer inhibitor of human rNAT1 than of hamster rNAT2.	dihydrofolate	0-17	N-acetyltransferase 1	Rattus norvegicus	61-66
15755837-2	2005	Dihydrofolate reductase (DHFR) is required to convert the folic acid used in supplements and for food fortification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced folate forms used by the cell.	dihydrofolate	124-137	dihydrofolate reductase	Homo sapiens	0-23
15755837-2	2005	Dihydrofolate reductase (DHFR) is required to convert the folic acid used in supplements and for food fortification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced folate forms used by the cell.	dihydrofolate	124-137	dihydrofolate reductase	Homo sapiens	25-29
15755837-2	2005	Dihydrofolate reductase (DHFR) is required to convert the folic acid used in supplements and for food fortification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced folate forms used by the cell.	dihydrofolate	124-137	thymidylate synthetase	Homo sapiens	150-170
15781612-3	2005	EGCG exhibited kinetics characteristic of a slow, tight-binding inhibitor of 7,8-dihydrofolate reduction with bovine liver DHFR (K(I) = 0.109 micromol/L), but of a classic, reversible, competitive inhibitor with chicken liver DHFR (K(I) = 10.3 micromol/L).	dihydrofolate	77-94	dihydrofolate reductase	Bos taurus	123-127
16003948-10	2005	Dihydrofolic acid (DHF) was a much poorer inhibitor of human rNAT1 than of hamster rNAT2.	dihydrofolate	0-17	N-acetyltransferase 2	Rattus norvegicus	83-88
14978269-1	2004	The interaction of dihydrofolate (H(2)F) and NADPH with a fluorescent derivative of H(2)F reductase (DHFR) was studied by using transient and single-molecule techniques.	dihydrofolate	19-32	dihydrofolate reductase	Homo sapiens	101-105
15251211-1	2004	Dihydropteroate synthase (DHPS) can metabolise sulfa drugs into sulfa-dihydropteroate (sulfa-DHP), which inhibits cell growth through competition with dihydrofolate (DHF), possibly indicating dihydrofolate reductase (DHFR) as the target of sulfa-DHP.	dihydrofolate	151-164	dihydrofolate reductase	Saccharomyces cerevisiae S288C	192-215
15251211-1	2004	Dihydropteroate synthase (DHPS) can metabolise sulfa drugs into sulfa-dihydropteroate (sulfa-DHP), which inhibits cell growth through competition with dihydrofolate (DHF), possibly indicating dihydrofolate reductase (DHFR) as the target of sulfa-DHP.	dihydrofolate	151-164	dihydrofolate reductase	Saccharomyces cerevisiae S288C	217-221
15251211-1	2004	Dihydropteroate synthase (DHPS) can metabolise sulfa drugs into sulfa-dihydropteroate (sulfa-DHP), which inhibits cell growth through competition with dihydrofolate (DHF), possibly indicating dihydrofolate reductase (DHFR) as the target of sulfa-DHP.	dihydrofolate	166-169	dihydrofolate reductase	Saccharomyces cerevisiae S288C	192-215
15251211-1	2004	Dihydropteroate synthase (DHPS) can metabolise sulfa drugs into sulfa-dihydropteroate (sulfa-DHP), which inhibits cell growth through competition with dihydrofolate (DHF), possibly indicating dihydrofolate reductase (DHFR) as the target of sulfa-DHP.	dihydrofolate	166-169	dihydrofolate reductase	Saccharomyces cerevisiae S288C	217-221
15213241-1	2004	To address the effects of ligand binding on the structural fluctuations of Escherichia coli dihydrofolate reductase (DHFR), the hydrogen/deuterium (H/D) exchange kinetics of its binary and ternary complexes formed with various ligands (folate, dihydrofolate, tetrahydrofolate, NADPH, NADP(+), and methotrexate) were examined using electrospray ionization mass spectrometry.	dihydrofolate	92-105	Dihydrofolate reductase	Escherichia coli	117-121
15115391-2	2004	The ability of the new analogues to inhibit reduction of dihydrofolate to tetrahydrofolate by Pc, Tg, Ma, and rat DHFR was determined, and the selectivity index (SI) was calculated from the ratio IC(50)(rat DHFR)/IC(50)(Pc, Tg, or Ma DHFR).	dihydrofolate	57-70	dihydrofolate reductase	Rattus norvegicus	114-118
15609999-5	2004	Spectra were recorded for binary and ternary complexes of wild-type DHFR bound to the substrate dihydrofolate (DHF), the product tetrahydrofolate (THF), the pseudosubstrate folate, reduced and oxidized NADPH cofactor, and the inactive cofactor analogue 5,6-dihydroNADPH.	dihydrofolate	96-109	Dihydrofolate reductase	Escherichia coli	68-72
12765545-1	2003	DHFR (dihydrofolate reductase) catalyses the metabolically important reduction of 7,8-dihydrofolate by NADPH.	dihydrofolate	82-99	Dihydrofolate reductase	Escherichia coli	0-4
12765545-1	2003	DHFR (dihydrofolate reductase) catalyses the metabolically important reduction of 7,8-dihydrofolate by NADPH.	dihydrofolate	82-99	Dihydrofolate reductase	Escherichia coli	6-29
12852950-3	2003	Secondary screening of these revealed twelve molecules that were competitive with dihydrofolate, nine of which have not been previously characterized as inhibitors of dihydrofolate reductase.	dihydrofolate	82-95	Dihydrofolate reductase	Escherichia coli	167-190
12359216-3	2002	The K(m) value of HHV-8 DHFR for dihydrofolate (DHF) was 2.02+/-0.44 microM, that of HVS DHFR was 4.31+/-0.56 microM, and that of RRV DHFR is 7.09+/-0.11 microM.	dihydrofolate	33-46	dihydrofolate reductase	Saimiriine gammaherpesvirus 2	24-28
12660990-1	2003	Despite much work, many key aspects of the mechanism of the dihydrofolate reductase (DHFR) catalyzed reduction of dihydrofolate remain unresolved.	dihydrofolate	60-73	dihydrofolate reductase	Gallus gallus	85-89
12660990-5	2003	MD simulations of chicken DHFR complexed with substrates and cofactor revealed a closing of the side chain of Tyr 31 over the active site on binding of dihydrofolate.	dihydrofolate	152-165	dihydrofolate reductase	Gallus gallus	26-30
12660990-11	2003	These results indicated that water can serve as the Broensted acid for the protonation of N5 of dihydrofolate during the DHFR catalyzed reduction.	dihydrofolate	96-109	dihydrofolate reductase	Gallus gallus	121-125
12862454-1	2003	Dihydrofolate Reductase (DHFR) catalyzes the reduction of dihydrofolate (H2F) to tetrahydrofolate.	dihydrofolate	58-71	Dihydrofolate reductase	Escherichia coli	0-23
12862454-1	2003	Dihydrofolate Reductase (DHFR) catalyzes the reduction of dihydrofolate (H2F) to tetrahydrofolate.	dihydrofolate	58-71	Dihydrofolate reductase	Escherichia coli	25-29
12756296-1	2003	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate.	dihydrofolate	58-71	Dihydrofolate reductase	Escherichia coli	0-23
12756296-1	2003	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate.	dihydrofolate	58-71	Dihydrofolate reductase	Escherichia coli	25-29
12732354-2	2003	In spectrophotometric assays of the kinetics of the reduction of dihydrofolate by DHFR in the presence of NADPH, these compounds had K(i) values ranging from 0.2 to 1.3pM, and thus were not greatly different in potency from the parent drug PT523.	dihydrofolate	65-78	dihydrofolate reductase	Homo sapiens	82-86
12628490-7	2003	For 2008/MRP1 and 2008/MRP3 cells FA growth stimulation capacity was dramatically decreased when, during a 4 hr exposure, metabolism into rapidly polyglutamatable and retainable dihydrofolate was blocked by the dihydrofolate reductase inhibitor trimetrexate.	dihydrofolate	178-191	ATP binding cassette subfamily C member 1	Homo sapiens	9-13
12628490-7	2003	For 2008/MRP1 and 2008/MRP3 cells FA growth stimulation capacity was dramatically decreased when, during a 4 hr exposure, metabolism into rapidly polyglutamatable and retainable dihydrofolate was blocked by the dihydrofolate reductase inhibitor trimetrexate.	dihydrofolate	178-191	ATP binding cassette subfamily C member 3	Homo sapiens	23-27
10584062-1	1999	We have investigated the importance of polarization by the enzyme dihydrofolate reductase (DHFR) on its substrates, folate and dihydrofolate, using a series of quantum mechanical (QM) techniques (Hartree-Fock (HF), Moller-Plesset second-order perturbation theory (MP2), local density approximation (LDA) and generalized gradient approximation (GGA) density functional theory (DFT) calculations) in which the bulk enzyme is included in the calculations as point charges.	dihydrofolate	66-79	dihydrofolate reductase	Homo sapiens	91-95
12021443-1	2002	Dihydrofolate reductase (DHFR) catalyzes the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of 7,8-dihydrofolate (H2F) to 5,6,7,8-tetrahydrofolate (H4F).	dihydrofolate	120-137	Dihydrofolate reductase	Escherichia coli	0-23
12021443-1	2002	Dihydrofolate reductase (DHFR) catalyzes the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of 7,8-dihydrofolate (H2F) to 5,6,7,8-tetrahydrofolate (H4F).	dihydrofolate	120-137	Dihydrofolate reductase	Escherichia coli	25-29
11989624-3	2001	This homotetrameric protein exhibits 222 symmetry, with only a few residues from each chain contributing to the active site, so related sites must be used to bind both substrate (dihydrofolate) and cofactor (NADPH) in the productive R67 DHFR.NADPH.dihydrofolate complex.	dihydrofolate	179-192	dihydrofolate reductase	Homo sapiens	237-241
11989624-3	2001	This homotetrameric protein exhibits 222 symmetry, with only a few residues from each chain contributing to the active site, so related sites must be used to bind both substrate (dihydrofolate) and cofactor (NADPH) in the productive R67 DHFR.NADPH.dihydrofolate complex.	dihydrofolate	248-261	dihydrofolate reductase	Homo sapiens	237-241
11560482-16	2001	For example, the Y69F R67 DHFR displays an 8-fold increase in the K(m) for dihydrofolate and a 20-fold increase in the K(m) for NADPH.	dihydrofolate	75-88	dihydrofolate reductase	Homo sapiens	26-30
11472112-1	2001	Despite much experimental and computational study, key aspects of the mechanism of reduction of dihydrofolate (DHF) by dihydrofolate reductase (DHFR) remain unresolved, while the secondary DHFR-catalyzed reduction of folate has been little studied.	dihydrofolate	96-109	Dihydrofolate reductase	Escherichia coli	119-142
11472112-1	2001	Despite much experimental and computational study, key aspects of the mechanism of reduction of dihydrofolate (DHF) by dihydrofolate reductase (DHFR) remain unresolved, while the secondary DHFR-catalyzed reduction of folate has been little studied.	dihydrofolate	96-109	Dihydrofolate reductase	Escherichia coli	144-148
11472112-1	2001	Despite much experimental and computational study, key aspects of the mechanism of reduction of dihydrofolate (DHF) by dihydrofolate reductase (DHFR) remain unresolved, while the secondary DHFR-catalyzed reduction of folate has been little studied.	dihydrofolate	96-109	Dihydrofolate reductase	Escherichia coli	189-193
11472112-1	2001	Despite much experimental and computational study, key aspects of the mechanism of reduction of dihydrofolate (DHF) by dihydrofolate reductase (DHFR) remain unresolved, while the secondary DHFR-catalyzed reduction of folate has been little studied.	dihydrofolate	111-114	Dihydrofolate reductase	Escherichia coli	119-142
11472112-1	2001	Despite much experimental and computational study, key aspects of the mechanism of reduction of dihydrofolate (DHF) by dihydrofolate reductase (DHFR) remain unresolved, while the secondary DHFR-catalyzed reduction of folate has been little studied.	dihydrofolate	111-114	Dihydrofolate reductase	Escherichia coli	144-148
11472112-1	2001	Despite much experimental and computational study, key aspects of the mechanism of reduction of dihydrofolate (DHF) by dihydrofolate reductase (DHFR) remain unresolved, while the secondary DHFR-catalyzed reduction of folate has been little studied.	dihydrofolate	111-114	Dihydrofolate reductase	Escherichia coli	189-193
11931624-3	2002	In a spectrophotometric assay of dihydrofolate reductase (DHFR) inhibition using dihydrofolate and NADPH as the cosubstrates, the previously unreported compounds 2 and the mixed 10R and 10S diastereomers of 6 had K(i) values of 0.21 +/- 0.05 pM and 0.60 +/- 0.02 pM, respectively, as compared with previously reported values of 3.70 +/- 0.35 pM for AMT and 0.33 +/- 0.04 pM for PT523.	dihydrofolate	33-46	dihydrofolate reductase	Homo sapiens	58-62
11679579-1	2001	R67 is a Type II dihydrofolate reductase (DHFR) that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate by facilitating the addition of a proton to N5 of DHF and the transfer of a hydride ion from NADPH to C6.	dihydrofolate	17-30	dihydrofolate reductase	Escherichia coli	42-46
11679579-1	2001	R67 is a Type II dihydrofolate reductase (DHFR) that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate by facilitating the addition of a proton to N5 of DHF and the transfer of a hydride ion from NADPH to C6.	dihydrofolate	95-98	dihydrofolate reductase	Escherichia coli	42-46
11679579-3	2001	Here, Raman difference measurements, conducted on the ternary complex of R67.NADP(+).DHF believed to be an accurate mimic of the productive DHFR.NADPH.DHF complex, show that the pK(a) of N5 in the complex is less than 4.	dihydrofolate	85-88	dihydrofolate reductase	Escherichia coli	140-144
10862611-6	2000	Again, methotrexate abolished the lysosomal uptake of the fusion protein, which was partially restored by washing of methotrexate from DHFR or by adding together methotrexate and dihydrofolate, the natural substrate of DHFR.	dihydrofolate	179-192	dihydrofolate reductase	Rattus norvegicus	219-223
10799479-5	2000	We show that dihydrofolate synthetase catalyzing the binding of the first glutamyl side chain to dihydropteroate yielding dihydrofolate is encoded by the YMR113w gene that we propose to rename FOL3.	dihydrofolate	13-26	dihydrofolate synthase	Saccharomyces cerevisiae S288C	193-197
10683342-5	2000	The K(m) of KSHV-DHFR for dihydrofolate (FH(2)) was 2.4 microM, which is significantly higher than the K(m) of recombinant hDHFR (rhDHFR) for FH(2) (390 nM).	dihydrofolate	26-39	dihydrofolate reductase	Homo sapiens	17-21
9543003-9	1997	Substantial substrate and cofactor inhibition are observed during catalysis, consistent with non-productive binding of either two DHF or two NADPH molecules in Q67H R67 DHFR.	dihydrofolate	130-133	dihydrofolate reductase	Homo sapiens	169-173
10415082-6	1999	This value of 1 nM allowed us to control the conversion from dihydrofolate (H(2)folate) to H(4)folate less than 10% of initial substrate concentrations during assay, when we used a concentration around K(m) values reported for DHFR from various sources.	dihydrofolate	61-74	dihydrofolate reductase	Homo sapiens	227-231
9526565-3	1998	The products were tested as competitive inhibitors of the reduction of dihydrofolate by Pneumocystis carinii, Toxoplasma gondii, and rat liver DHFR.	dihydrofolate	71-84	dihydrofolate reductase	Rattus norvegicus	143-147
8852336-2	1995	The primary target of MTX is the enzyme dihydrofolate reductase (DHFR) which catalyzes the reduction of folate and 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate.	dihydrofolate	115-132	dihydrofolate reductase	Homo sapiens	40-63
9056490-6	1997	The steady-state kinetic parameters, dissociation constants for binary complexes of dihydrofolate, NADPH, and methotrexate with ch-DHFR, and the inhibitor constant of methotrexate have also been determined.	dihydrofolate	84-97	dihydrofolate reductase	Escherichia coli	131-135
8999931-12	1997	These results indicate protonated dihydrofolate (pKa = 2.59) is the productive substrate and that R67 DHFR does not possess a proton donor.	dihydrofolate	34-47	dihydrofolate reductase	Homo sapiens	102-106
8978793-2	1996	Methotrexate tightly binds to dihydrofolate reductase (DHFR), blocking the reduction of dihydrofolate to tetrahydrofolic acid, the active form of folic acid.	dihydrofolate	30-43	dihydrofolate reductase	Homo sapiens	55-59
8845002-1	1996	The bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) carries out two distinct reactions, with the dihydrofolate produced by the TS-catalyzed reaction acting as the substrate for the DHFR-catalyzed reaction.	dihydrofolate	24-37	dihydrofolate reductase	Homo sapiens	70-74
8845002-1	1996	The bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) carries out two distinct reactions, with the dihydrofolate produced by the TS-catalyzed reaction acting as the substrate for the DHFR-catalyzed reaction.	dihydrofolate	24-37	dihydrofolate reductase	Homo sapiens	208-212
8852336-2	1995	The primary target of MTX is the enzyme dihydrofolate reductase (DHFR) which catalyzes the reduction of folate and 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate.	dihydrofolate	115-132	dihydrofolate reductase	Homo sapiens	65-69
8490020-3	1993	Incubation of DHFR protein with either its substrates, dihydrofolate or NADPH, or with an inhibitor, methotrexate, repressed its ability to interact with DHFR mRNA.	dihydrofolate	55-68	dihydrofolate reductase	Homo sapiens	154-158
8003467-0	1994	Determination by Raman spectroscopy of the pKa of N5 of dihydrofolate bound to dihydrofolate reductase: mechanistic implications.	dihydrofolate	56-69	Dihydrofolate reductase	Escherichia coli	79-102
8003467-1	1994	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (H2folate) to tetrahydrofolate by NADPH, and this requires that the pteridine ring be protonated at N5.	dihydrofolate	58-71	Dihydrofolate reductase	Escherichia coli	0-23
8003467-1	1994	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (H2folate) to tetrahydrofolate by NADPH, and this requires that the pteridine ring be protonated at N5.	dihydrofolate	58-71	Dihydrofolate reductase	Escherichia coli	25-29
8003467-3	1994	We have determined the pKa of N5 of dihydrofolate in the Escherichia coli DHFR/NADP+/H2folate ternary complex by Raman difference spectroscopy and found that the value is 6.5.	dihydrofolate	36-49	Dihydrofolate reductase	Escherichia coli	74-78
8226776-8	1993	The protein product, R67 DHFRdouble, is twice the molecular mass of native R67 DHFR and is fully active with kcat = 1.2 s-1, Km(NADPH) = 2.7 microM and Km(dihydrofolate) = 6.3 microM.	dihydrofolate	155-168	dihydrofolate reductase	Homo sapiens	25-29
8490020-3	1993	Incubation of DHFR protein with either its substrates, dihydrofolate or NADPH, or with an inhibitor, methotrexate, repressed its ability to interact with DHFR mRNA.	dihydrofolate	55-68	dihydrofolate reductase	Homo sapiens	14-18
8461309-4	1993	D27S+F153S and D27S+I155N DHFRs display 2-3-fold increases in kcat over D27S DHFR values, but only the F153S mutation decreases the Km for dihydrofolate by a factor of 2.	dihydrofolate	139-152	Dihydrofolate reductase	Escherichia coli	26-30
8461049-3	1993	FdUMP binding to TS was also stimulated by tetrahydrofolate and dihydrofolate (85% and 30% as compared to (6RS)-CH2-H4-folate, respectively), but not by the stereoisomers of 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate (leucovorin).	dihydrofolate	64-77	thymidylate synthetase	Homo sapiens	17-19
1427091-5	1992	The inability of the mutants to metabolize FA suggests that the DFR1 gene product may have a role in folate metabolism in addition to its well-characterized function in the reduction of dihydrofolate.	dihydrofolate	186-199	dihydrofolate reductase	Saccharomyces cerevisiae S288C	64-68
1281316-4	1992	The protein product had the expected size (18 kDa) and catalyzed the NADPH-dependent reduction of 7,8-dihydrofolic acid to 5,6,7,8-tetrahydrofolic acid as efficiently as authentic DHFR.	dihydrofolate	98-119	dihydrofolate reductase	Oryctolagus cuniculus	180-184
1637816-1	1992	The kinetics of the NADPH-dependent reduction of 7,8-dihydrofolate, folate, and 7,8-dihydrobiopterin by human dihydrofolate reductase have been examined over the pH range from 4.0 to 9.5.	dihydrofolate	49-66	dihydrofolate reductase	Homo sapiens	110-133
1385949-0	1992	Interconversion of tetrahydrofolate cofactors to dihydrofolate induced by trimetrexate after suppression of thymidylate synthase by fluorodeoxyuridine in L1210 leukemia cells.	dihydrofolate	49-62	thymidylate synthase	Mus musculus	108-128
1385949-3	1992	In the present study, we assessed the rate of resumption of thymidylate synthase catalytic activity in terms of [3H]deoxyuridine incorporation into DNA and dihydrofolate generation from tetrahydrofolate cofactors following exposure of cells to fluorodeoxyuridine.	dihydrofolate	156-169	thymidylate synthase	Mus musculus	60-80
1613754-10	1992	Kinetic studies with rat liver DHFR show that MBP is an inhibitor that competes with NADPH as well as dihydrofolate.	dihydrofolate	102-115	dihydrofolate reductase	Rattus norvegicus	31-35
1907850-5	1991	At this pH, the KD value for dihydrofolate (FAH2) for the R70K enzyme shows only a 7-fold increase over that for the wild-type hDHFR.	dihydrofolate	29-42	dihydrofolate reductase	Homo sapiens	127-132
1314649-4	1992	koff for dissociation of folate, dihydrofolate (H2folate), and H4folate from their binary complexes with hDHFR is similarly pH dependent.	dihydrofolate	33-46	dihydrofolate reductase	Homo sapiens	105-110
1929292-5	1991	The standard assay for P. carinii dihydrofolate reductase contained 0.12 mM NADPH and 92 microM dihydrofolic acid.	dihydrofolate	96-113	dihydrofolate reductase	Homo sapiens	34-57
2247056-1	1990	Replication of the Chinese hamster dihydrofolate (dhfr) gene initiates near a 281-bp HaeIII fragment of stably bent DNA that binds RIP60, a 60-kDa origin-specific DNA-binding protein that has been purified from HeLa cell nuclear extract (L. Dailey, M. S. Caddle, N. Heintz, and N. H. Heintz, Mol.	dihydrofolate	35-48	replication initiator 1	Homo sapiens	131-136
1904273-9	1991	The Km value for human DHFR for the dihydrofolate analogue is 2.0 microM.	dihydrofolate	36-49	dihydrofolate reductase	Homo sapiens	23-27
1961697-1	1991	Escherichia coli dihydrofolate reductase (DHFR) carries a net charge of -10 electrons yet it binds ligands with net charges of -4 (NADPH) and -2 (folate or dihydrofolate).	dihydrofolate	17-30	Dihydrofolate reductase	Escherichia coli	42-46
1825652-0	1991	Effect of direct suppression of thymidylate synthase at the 5,10-methylenetetrahydrofolate binding site on the interconversion of tetrahydrofolate cofactors to dihydrofolate by antifolates.	dihydrofolate	160-173	thymidylate synthetase	Homo sapiens	32-52
1825652-10	1991	Network thermodynamic simulations predict, and experiments verify, that inhibition of thymidylate synthase at the 5,10-methylenetetrahydrofolate site by PD130883, when dihydrofolate reductase is only partially suppressed (approximately 85%) with 0.1 microM trimetrexate, substantially decreases (31-47%) the net level of interconversion of tetrahydrofolate cofactors to dihydrofolate.	dihydrofolate	168-181	thymidylate synthetase	Homo sapiens	86-106
1825652-11	1991	Further computer simulations predict that under conditions in which residual dihydrofolate reductase activity persists within the cells (more than about 5%), feedback inhibitory effects of dihydrofolate polyglutamates as well as other weak inhibitors of thymidylate synthase can significantly limit the extent of net interconversion of tetrahydrofolate cofactors to dihydrofolate and produce an apparent "compartmentation phenomenon" in which tetrahydrofolate cofactor pools are preserved within the cell in the presence of antifolates.	dihydrofolate	77-90	thymidylate synthetase	Homo sapiens	254-274
2271620-9	1990	RBG200 DHFR was found to specifically transfer the pro-R hydrogen of NADPH to dihydrofolate, making it a member of the A-stereospecific class of dehydrogenases.	dihydrofolate	78-91	dihydrofolate reductase	Homo sapiens	7-11
2730668-1	1989	The significance of the enol form of the pterin ring in enzymatic reduction of dihydrofolate by DHFR is discussed on the basis of the results of ab initio calculations carried out on the keto/enol tautomers of 6-methyl-7, 8-dihydropterin as the model compound for the natural substrate, dihydrofolate.	dihydrofolate	79-92	dihydrofolate reductase	Homo sapiens	96-100
2168155-7	1990	NaHCO3 also activated FPGS activity when folic acid, dihydrofolic acid and tetrahydrofolic acid were substrates.	dihydrofolate	53-70	folylpolyglutamate synthase	Homo sapiens	22-26
34788822-3	2022	The reduction of FA to dihydrofolate by dihydrofolate reductase (DHFR) is slow in humans.	dihydrofolate	23-36	dihydrofolate reductase	Homo sapiens	40-63
34788822-3	2022	The reduction of FA to dihydrofolate by dihydrofolate reductase (DHFR) is slow in humans.	dihydrofolate	23-36	dihydrofolate reductase	Homo sapiens	65-69
2529254-8	1989	This is consistent with computer simulations which predict that direct inhibition of thymidylate synthase by 97, 98, and 99% should increase the half-time of dihydrofolate rise after trimetrexate to 40, 60, and 124 min, respectively, but the final level achieved is always the same as in cells with normal thymidylate synthase activity.	dihydrofolate	158-171	thymidylate synthase	Mus musculus	85-105
2529254-8	1989	This is consistent with computer simulations which predict that direct inhibition of thymidylate synthase by 97, 98, and 99% should increase the half-time of dihydrofolate rise after trimetrexate to 40, 60, and 124 min, respectively, but the final level achieved is always the same as in cells with normal thymidylate synthase activity.	dihydrofolate	158-171	thymidylate synthase	Mus musculus	306-326
2502633-6	1989	Those compounds that had basic substituents in the 2-position of the quinoline ring were also highly specific for bacterial dihydrofolate DHFR, relative to a vertebrate counterpart.	dihydrofolate	124-137	Dihydrofolate reductase	Escherichia coli	138-142
2354716-6	1990	P. carinii DHFR could be easily distinguished from rat DHFR, which is similar in size, by the differences in Km for dihydrofolate (P. carinii, 17.6 +/- 3.9 microM; rat, 4.0 +/- 2.2 microM).	dihydrofolate	116-129	dihydrofolate reductase	Rattus norvegicus	11-15
2341391-5	1990	The inhibition of thymidylate synthesis coincided temporally with the rapid intracellular accumulation of H2PteGlu, a known inhibitor of thymidylate synthase.	dihydrofolate	106-114	thymidylate synthetase	Homo sapiens	137-157
2529254-10	1989	The model predicts, and the data demonstrate, that virtually any residual thymidylate synthase activity will permit the interconversion of all tetrahydrofolate cofactors available for oxidation to dihydrofolate when dihydrofolate reductase activity is abolished, but the rate of interconversion will be slowed.	dihydrofolate	197-210	thymidylate synthase	Mus musculus	74-94
2529254-12	1989	These data exclude the possibility that direct inhibition of thymidylate synthase by dihydrofolate polyglutamates, or any other intracellular folates that accumulate in cells after antifolates, can account for the rapid but partial interconversion of reduced folate cofactors to dihydrofolate.	dihydrofolate	85-98	thymidylate synthase	Mus musculus	61-81
2730668-1	1989	The significance of the enol form of the pterin ring in enzymatic reduction of dihydrofolate by DHFR is discussed on the basis of the results of ab initio calculations carried out on the keto/enol tautomers of 6-methyl-7, 8-dihydropterin as the model compound for the natural substrate, dihydrofolate.	dihydrofolate	287-300	dihydrofolate reductase	Homo sapiens	96-100
2765506-2	1989	This substitution was of interest in view of earlier chemical modification studies (Kumar et al., 1981) and structural studies based on X-ray crystallographic data (Matthews et al., 1985a,b) which had implicated the corresponding residue in chicken liver DHFR, Tyr-31, in the binding of dihydrofolate.	dihydrofolate	287-300	dihydrofolate reductase	Gallus gallus	255-259
2448654-6	1987	Important elements in leucovorin rescue are reactivation of DHFR with depression of cellular dihydrofolate (FH2) and provision of folate substrate to circumvent the block in FH4 synthesis.	dihydrofolate	93-106	dihydrofolate reductase	Homo sapiens	60-64
2744204-6	1989	The dissociation constants (Kd) of MTX, FMTX, NADPH and 7,8-dihydrofolate (DHF) from bovine liver DHFR have been determined by fluorometric titrations.	dihydrofolate	56-73	dihydrofolate reductase	Bos taurus	98-102
2744204-6	1989	The dissociation constants (Kd) of MTX, FMTX, NADPH and 7,8-dihydrofolate (DHF) from bovine liver DHFR have been determined by fluorometric titrations.	dihydrofolate	75-78	dihydrofolate reductase	Bos taurus	98-102
3052577-8	1988	As NADPH and dihydrofolate function as activators and as NADPH behaves as a sticky substrate, the kinetic mechanism of the dihydrofolate reductase reaction with the natural substrates is steady-state random.	dihydrofolate	13-26	Dihydrofolate reductase	Escherichia coli	123-146
3275776-2	1988	A strictly conserved residue at the dihydrofolate binding site of DHFR, phenylalanine-31, has been replaced with tyrosine or valine to ascertain the importance for binding of this hydrophobic amino acid, which interacts with both the pteridine ring and the p-aminobenzoyl moiety.	dihydrofolate	36-49	Dihydrofolate reductase	Escherichia coli	66-70
2443493-5	1987	The inhibition of purine synthesis coincides with the rapid intracellular accumulation of H2PteGlu, a known inhibitor of AICAR transformylase.	dihydrofolate	90-98	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	121-126
3587364-1	1987	In previous work, several methotrexate (MTX)-resistant variants were isolated frm the human cell line HeLa BU25, which exhibited a high degree of dihydrofolate (DHFR) gene amplification (estimated to be 250- to 300-fold).	dihydrofolate	146-159	dihydrofolate reductase	Homo sapiens	161-165
24306990-5	1985	The carrot DHFR is characterized by a pH optimum of 5.9, Km values for dihydrofolate and NADPH of 3.7 muM and 2.2 muM, respectively and a turnover number of 4 750 or 1 500 when referring to the 183 K form or the 58 K monomer, respectively.	dihydrofolate	71-84	dihydrofolate reductase	Homo sapiens	11-15
2428470-0	1986	Interaction of polyglutamyl derivatives of methotrexate, 10-deazaaminopterin, and dihydrofolate with dihydrofolate reductase.	dihydrofolate	82-95	dihydrofolate reductase	Ovis aries	101-124
2428470-10	1986	We conclude that polyglutamylation can alter the interaction of folate analogues and dihydrofolate with DHFR.	dihydrofolate	85-98	dihydrofolate reductase	Ovis aries	104-108
6433972-0	1984	Dismutation of dihydrofolate by dihydrofolate reductase.	dihydrofolate	15-28	dihydrofolate reductase	Bos taurus	32-55
3883353-2	1985	The method is illustrated by the cloning of several mutant genes as well as the wild-type gene for Chinese hamster dihydrofolate reductase (DHFR; 7,8-dihydrofolate:NADP+ oxidoreductase, EC 1.5.1.3).	dihydrofolate	146-163	dihydrofolate reductase	Cricetulus griseus	115-138
3883353-2	1985	The method is illustrated by the cloning of several mutant genes as well as the wild-type gene for Chinese hamster dihydrofolate reductase (DHFR; 7,8-dihydrofolate:NADP+ oxidoreductase, EC 1.5.1.3).	dihydrofolate	146-163	dihydrofolate reductase	Cricetulus griseus	140-144
6433972-1	1984	Degradation of 7,8-dihydrofolate (H2folate) in the presence of dihydrofolate reductase (DHFR) has been shown due not to an oxygenase activity of the reductase as previously reported but to dismutation of H2folate to folate and 5,6,7,8-tetrahydrofolate (H4folate).	dihydrofolate	15-32	dihydrofolate reductase	Bos taurus	63-86
6433972-1	1984	Degradation of 7,8-dihydrofolate (H2folate) in the presence of dihydrofolate reductase (DHFR) has been shown due not to an oxygenase activity of the reductase as previously reported but to dismutation of H2folate to folate and 5,6,7,8-tetrahydrofolate (H4folate).	dihydrofolate	15-32	dihydrofolate reductase	Bos taurus	88-92
7051769-0	1982	Modulation of methylenetetrahydrofolate reductase activity by S-adenosylmethionine and by dihydrofolate and its polyglutamate analogues.	dihydrofolate	90-103	methylenetetrahydrofolate reductase	Homo sapiens	14-49
6882460-7	1983	The observation that NADH supports the reduction of folate and dihydrofolate but not MTX binding suggests that natural resistance to MTX could exist if NADH replaces NADPH as the main cofactor for DHFR.	dihydrofolate	63-76	dihydrofolate reductase	Homo sapiens	197-201
6189586-5	1983	Addition of 5-fluoro-2"-deoxyuridine had no effect on this response to the reduced folate, thereby precluding a direct role for the thymidylate synthase-dependent generation of dihydrofolate in this dissociation of methotrexate from dihydrofolate reductase.	dihydrofolate	177-190	thymidylate synthase	Mus musculus	132-152
7051769-7	1982	Methylenetetrahydrofolate reductase is inhibited by dihydrofolate and its polyglutamate analogues.	dihydrofolate	52-65	methylenetetrahydrofolate reductase	Homo sapiens	0-35
7051769-10	1982	We propose that stimulation of thymidylate synthase activity (as in the replicating cell) may lead to elevations in the steady state levels of cellular dihydrofolate derivatives and to resultant inhibition of methylenetetrahydrofolate reductase activity.	dihydrofolate	152-165	thymidylate synthetase	Homo sapiens	31-51
293670-1	1979	Selection of mammalian cells in progressively increasing concentrations of methotrexate results in selective amplification of DNA sequences coding for dihydrofolate reductase (tetrahydrofolate dehydrogenase, 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3).	dihydrofolate	151-164	thioredoxin reductase 1	Homo sapiens	239-253
6990970-1	1980	Dihydrofolate and dihydropteroylpolyglutamates inhibit pig liver methylenetetrahydrofolate reductase.	dihydrofolate	0-13	methylenetetrahydrofolate reductase	Sus scrofa	65-100
7011378-1	1981	Reduced nicotinamide adenine dinucleotide phosphate (NADPH), folate, dihydrofolate, and the inhibitors trimethoprim and methotrexate bind rapidly and reversibly to both dihydrofolate reductase isoenzymes isolated from Escherichia coli RT500.	dihydrofolate	69-82	Dihydrofolate reductase	Escherichia coli	169-192
32051770-3	2019	Here, we examined dihydrofolate reductase (DHFR), an enzyme that catalyzes hydride from C4" of NADPH to C6 of 7,8-dihydrofolate (H2F).	dihydrofolate	110-127	dihydrofolate reductase	Homo sapiens	18-41
912881-2	1977	In the presence of dihydrofolate reductase (EC 1.5.1.3), dihydrofolic acid is converted to tetrahydrofolate.	dihydrofolate	57-74	dihydrofolate reductase	Homo sapiens	19-42
33315225-3	2021	DHFR is an essential enzyme that catalyzes the reduction of dihydrofolate to tetrahydrofolate.	dihydrofolate	60-73	dihydrofolate reductase	Homo sapiens	0-4
508720-0	1979	Inhibition of pig liver methylenetetrahydrofolate reductase by dihydrofolate: some mechanistic and regulatory implications.	dihydrofolate	63-76	methylenetetrahydrofolate reductase	Sus scrofa	24-59
1277151-16	1976	Dihydrofolate or 5,10-methylenetetrahydrofolate, at 10(-3) M, only partially protected thymidylate synthetase.	dihydrofolate	0-13	thymidylate synthetase	Homo sapiens	87-109
33724022-13	2021	For the two proteins that were experimentally tested, DHFR, a well-studied protein that catalyzes the conversion of dihydrofolate to tetrahydrofolate, and the kinase ACVR1, FRAGSITE identified new small-molecule nanomolar binders.	dihydrofolate	116-129	dihydrofolate reductase	Homo sapiens	54-58
33724022-13	2021	For the two proteins that were experimentally tested, DHFR, a well-studied protein that catalyzes the conversion of dihydrofolate to tetrahydrofolate, and the kinase ACVR1, FRAGSITE identified new small-molecule nanomolar binders.	dihydrofolate	116-129	activin A receptor type 1	Homo sapiens	166-171
32752079-2	2020	A known folate antagonist, methotrexate (MTX) inhibits human dihydrofolate reductase (hDHFR), the enzyme responsible for the catalysis of 7,8-dihydrofolate reduction to 5,6,7,8-tetrahydrofolate, in biosynthesis and cell proliferation.	dihydrofolate	138-155	dihydrofolate reductase	Homo sapiens	61-84
32752079-2	2020	A known folate antagonist, methotrexate (MTX) inhibits human dihydrofolate reductase (hDHFR), the enzyme responsible for the catalysis of 7,8-dihydrofolate reduction to 5,6,7,8-tetrahydrofolate, in biosynthesis and cell proliferation.	dihydrofolate	138-155	dihydrofolate reductase	Homo sapiens	86-91
32051770-3	2019	Here, we examined dihydrofolate reductase (DHFR), an enzyme that catalyzes hydride from C4" of NADPH to C6 of 7,8-dihydrofolate (H2F).	dihydrofolate	110-127	dihydrofolate reductase	Homo sapiens	43-47
30979096-1	2019	A class of gold(I) phosphane complexes have been identified as inhibitors of dihydrofolate reductase (DHFR) from E. coli, an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), using NADPH as a coenzyme.	dihydrofolate	77-90	Dihydrofolate reductase	Escherichia coli	102-106
31520592-5	2019	Furthermore, the tetrahydrofolate- and time-dependent, covalent binding by thymidylate synthase of each 5-fluoro-dUMP and N4-hydroxy-dCMP was shown to be accompanied by the enzyme inactivation, as well as spectrophotometrically confirmed dihydrofolate production, the latter demonstrated to depend on the reaction time, thymidylate synthase activity and temperature of the incubation mixture, further documenting its catalytic character.	dihydrofolate	238-251	thymidylate synthase	Mus musculus	75-95
31520592-5	2019	Furthermore, the tetrahydrofolate- and time-dependent, covalent binding by thymidylate synthase of each 5-fluoro-dUMP and N4-hydroxy-dCMP was shown to be accompanied by the enzyme inactivation, as well as spectrophotometrically confirmed dihydrofolate production, the latter demonstrated to depend on the reaction time, thymidylate synthase activity and temperature of the incubation mixture, further documenting its catalytic character.	dihydrofolate	238-251	thymidylate synthase	Mus musculus	320-340
31401334-2	2019	Dihydrofolate reductase (DHFR), an enzyme involved in folate metabolism converts dihydrofolate into tetrahydrofolate, which is required for the de novo synthesis of purines, and certain amino acids.	dihydrofolate	81-94	dihydrofolate reductase	Homo sapiens	0-23
31401334-2	2019	Dihydrofolate reductase (DHFR), an enzyme involved in folate metabolism converts dihydrofolate into tetrahydrofolate, which is required for the de novo synthesis of purines, and certain amino acids.	dihydrofolate	81-94	dihydrofolate reductase	Homo sapiens	25-29
31666629-6	2019	We showed that MMV675968 targeted A. baumannii dihydrofolate reductase (AbDHFR) as determined by an E. coli surrogate whose growth was dependent on AbDHFR function and by an in vitro DHFR activity assay.	dihydrofolate	47-60	dihydrofolate reductase	Escherichia coli	74-78
31289693-2	2019	Dihydrofolate Reductase from Thermotoga maritima (TmDFHFR) is a dimeric thermophilic enzyme that catalyzes the hydride transfer from the cofactor NADPH to dihydrofolate less efficiently than other DHFR enzymes, such as the mesophilic analogue Escherichia coli DHFR (EcDHFR).	dihydrofolate	155-168	dihydrofolate reductase	Escherichia coli	197-201
31289693-2	2019	Dihydrofolate Reductase from Thermotoga maritima (TmDFHFR) is a dimeric thermophilic enzyme that catalyzes the hydride transfer from the cofactor NADPH to dihydrofolate less efficiently than other DHFR enzymes, such as the mesophilic analogue Escherichia coli DHFR (EcDHFR).	dihydrofolate	155-168	dihydrofolate reductase	Escherichia coli	260-264
30979096-1	2019	A class of gold(I) phosphane complexes have been identified as inhibitors of dihydrofolate reductase (DHFR) from E. coli, an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), using NADPH as a coenzyme.	dihydrofolate	102-105	Dihydrofolate reductase	Escherichia coli	77-100
30754680-1	2019	Dihydrofolate reductase (DHFR) is an essential cellular enzyme and thereby catalyzes thereduction of dihydrofolate to tetrahydrofolate (THF).	dihydrofolate	101-114	dihydrofolate reductase	Homo sapiens	0-23
30724552-1	2019	Dihydrofolate reductase (DHFR) reduces dihydrofolate (DHF) to tetrahydrofolate using NADPH as a cofactor.	dihydrofolate	39-52	Dihydrofolate reductase	Escherichia coli	0-23
30724552-1	2019	Dihydrofolate reductase (DHFR) reduces dihydrofolate (DHF) to tetrahydrofolate using NADPH as a cofactor.	dihydrofolate	39-52	Dihydrofolate reductase	Escherichia coli	25-29
30724552-1	2019	Dihydrofolate reductase (DHFR) reduces dihydrofolate (DHF) to tetrahydrofolate using NADPH as a cofactor.	dihydrofolate	25-28	Dihydrofolate reductase	Escherichia coli	0-23
30508692-3	2019	The binding affinities of all these species (DHF, DHFP and THF) contribute to the mechanism of DHFR catalytic action.	dihydrofolate	45-48	dihydrofolate reductase	Homo sapiens	95-99
30754680-1	2019	Dihydrofolate reductase (DHFR) is an essential cellular enzyme and thereby catalyzes thereduction of dihydrofolate to tetrahydrofolate (THF).	dihydrofolate	101-114	dihydrofolate reductase	Homo sapiens	25-29
30564747-1	2018	Dihydrofolate reductase (DHFR) catalyzes the stereospecific reduction of 7,8-dihydrofolate (FH2) to (6s)-5,6,7,8-tetrahydrofolate (FH4) via hydride transfer from NADPH.	dihydrofolate	73-90	Dihydrofolate reductase	Escherichia coli	0-23
30564747-1	2018	Dihydrofolate reductase (DHFR) catalyzes the stereospecific reduction of 7,8-dihydrofolate (FH2) to (6s)-5,6,7,8-tetrahydrofolate (FH4) via hydride transfer from NADPH.	dihydrofolate	73-90	Dihydrofolate reductase	Escherichia coli	25-29
30019321-1	2018	The enzyme dihydrofolate reductase (DHFR) catalyzes NADPH dependent reduction of dihydrofolate to tetrahydrofolate.	dihydrofolate	11-24	dihydrofolate reductase	Homo sapiens	36-40
30040418-1	2018	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) in the presence of NADPH.	dihydrofolate	58-71	Dihydrofolate reductase	Escherichia coli	0-23
30040418-1	2018	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) in the presence of NADPH.	dihydrofolate	58-71	Dihydrofolate reductase	Escherichia coli	25-29
30040418-1	2018	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) in the presence of NADPH.	dihydrofolate	25-28	Dihydrofolate reductase	Escherichia coli	0-23
30398861-1	2018	In the present study, we address the effect of active site structure and dynamics of different dihydrofolate reductase (DHFR) isoforms on the p Ka of the bound substrate 7,8-dihydrofolate, in an attempt to understand possible evolutionary trends.	dihydrofolate	170-187	dihydrofolate reductase	Homo sapiens	95-118
30398861-1	2018	In the present study, we address the effect of active site structure and dynamics of different dihydrofolate reductase (DHFR) isoforms on the p Ka of the bound substrate 7,8-dihydrofolate, in an attempt to understand possible evolutionary trends.	dihydrofolate	170-187	dihydrofolate reductase	Homo sapiens	120-124
28594957-1	2017	In plants and protists, dihydrofolate reductase (DHFR) and thymidylate synthase (TS) are part of a bifunctional enzyme (DRTS) that allows efficient recycling of the dihydrofolate resulting from TS activity.	dihydrofolate	24-37	dihydrofolate reductase	Arabidopsis thaliana	49-53
28605138-7	2017	The molecular docking and Prime-MMGBSA calculations of the natural substrate (dihydrofolate, DHF) and classical DHFR inhibitor (methotrexate, MTX) were performed in protozoan DHFR enzymes.	dihydrofolate	78-91	dihydrofolate reductase	Homo sapiens	112-116
28605138-7	2017	The molecular docking and Prime-MMGBSA calculations of the natural substrate (dihydrofolate, DHF) and classical DHFR inhibitor (methotrexate, MTX) were performed in protozoan DHFR enzymes.	dihydrofolate	78-91	dihydrofolate reductase	Homo sapiens	175-179
28350247-1	2017	Dihydrofolate reductase (DHFR) reduces folic acid and recycles dihydrofolate generated during dTMP biosynthesis to tetrahydrofolate.	dihydrofolate	63-76	dihydrofolate reductase	Danio rerio	0-23
28350247-1	2017	Dihydrofolate reductase (DHFR) reduces folic acid and recycles dihydrofolate generated during dTMP biosynthesis to tetrahydrofolate.	dihydrofolate	63-76	dihydrofolate reductase	Danio rerio	25-29
24517487-1	2014	A weak association between osmolytes and dihydrofolate (DHF) decreases the affinity of the substrate for the Escherichia coli chromosomal and R67 plasmid dihydrofolate reductase (DHFR) enzymes.	dihydrofolate	41-54	Dihydrofolate reductase	Escherichia coli	154-177
27013776-3	2016	To be used, folic acid must be converted to 7,8-dihydrofolate by dihydrofolate reductase to generate one-carbon derivatives serving as important cellular cofactors in the synthesis of nucleotides and amino acids required for cell growth.	dihydrofolate	44-61	dihydrofolate reductase	Homo sapiens	65-88
26637016-10	2016	Computer simulations that restrain the dihydrofolate tail near K32 indicate that cross-linking still allows movement of the p-aminobenzoyl ring, which allows the reaction to occur.	dihydrofolate	39-52	keratin 32	Homo sapiens	63-66
26125523-1	2015	The stepwise reduction of dihydrofolate to tetrahydrofolate entails significant conformational changes of dihydrofolate reductase (DHFR).	dihydrofolate	26-39	dihydrofolate reductase	Homo sapiens	106-129
26125523-1	2015	The stepwise reduction of dihydrofolate to tetrahydrofolate entails significant conformational changes of dihydrofolate reductase (DHFR).	dihydrofolate	26-39	dihydrofolate reductase	Homo sapiens	131-135
28422217-2	2017	DHFR catalyzes the reduction of dihydrofolate to tetrahydrofolate, which is a precursor for purine and thymidylate synthesis.	dihydrofolate	32-45	Dihydrofolate reductase	Escherichia coli	0-4
25453083-1	2014	Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF).	dihydrofolate	74-87	Dihydrofolate reductase	Escherichia coli	0-23
25453083-1	2014	Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF).	dihydrofolate	74-87	Dihydrofolate reductase	Escherichia coli	25-29
25453083-1	2014	Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF).	dihydrofolate	25-28	Dihydrofolate reductase	Escherichia coli	0-23
24517487-1	2014	A weak association between osmolytes and dihydrofolate (DHF) decreases the affinity of the substrate for the Escherichia coli chromosomal and R67 plasmid dihydrofolate reductase (DHFR) enzymes.	dihydrofolate	41-54	Dihydrofolate reductase	Escherichia coli	179-183
24517487-1	2014	A weak association between osmolytes and dihydrofolate (DHF) decreases the affinity of the substrate for the Escherichia coli chromosomal and R67 plasmid dihydrofolate reductase (DHFR) enzymes.	dihydrofolate	56-59	Dihydrofolate reductase	Escherichia coli	154-177
24517487-1	2014	A weak association between osmolytes and dihydrofolate (DHF) decreases the affinity of the substrate for the Escherichia coli chromosomal and R67 plasmid dihydrofolate reductase (DHFR) enzymes.	dihydrofolate	56-59	Dihydrofolate reductase	Escherichia coli	179-183
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	155-161
24122410-0	2013	Insight into the molecular mechanism about lowered  dihydrofolate binding affinity to dihydrofolate reductase-like 1  (DHFRL1).	dihydrofolate	52-65	dihydrofolate reductase 2	Homo sapiens	86-116
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	292-298
24122410-0	2013	Insight into the molecular mechanism about lowered  dihydrofolate binding affinity to dihydrofolate reductase-like 1  (DHFRL1).	dihydrofolate	52-65	dihydrofolate reductase 2	Homo sapiens	119-125
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	292-298
24122410-2	2013	Although DHFRL1 have high sequence homology with human DHFR, dihydrofolate (DHF) exhibits a lowered binding affinity to DHFRL1 and the corresponding molecular mechanism is still unknown.	dihydrofolate	61-74	dihydrofolate reductase	Homo sapiens	9-13
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase	Homo sapiens	146-150
24122410-2	2013	Although DHFRL1 have high sequence homology with human DHFR, dihydrofolate (DHF) exhibits a lowered binding affinity to DHFRL1 and the corresponding molecular mechanism is still unknown.	dihydrofolate	61-74	dihydrofolate reductase 2	Homo sapiens	120-126
24122410-3	2013	To address this question, we studied the binding of DHF to DHFRL1 and DHFR by using molecular dynamics simulation.	dihydrofolate	52-55	dihydrofolate reductase 2	Homo sapiens	59-65
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	155-161
24122410-3	2013	To address this question, we studied the binding of DHF to DHFRL1 and DHFR by using molecular dynamics simulation.	dihydrofolate	52-55	dihydrofolate reductase	Homo sapiens	59-63
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	292-298
24122410-4	2013	Moreover, to investigate the role the 24th residue of DHFR/DHFRL1 plays in DHF binding, R24W DHFRL1 mutant was also studied.	dihydrofolate	54-57	dihydrofolate reductase 2	Homo sapiens	59-65
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	61-64	dihydrofolate reductase 2	Homo sapiens	155-161
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase	Homo sapiens	146-150
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	155-161
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	292-298
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	292-298
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase	Homo sapiens	146-150
24122410-5	2013	The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24.	dihydrofolate	116-119	dihydrofolate reductase 2	Homo sapiens	292-298
24122410-6	2013	The side chain of Arg24 in DHFRL1 can extend deeply into the binding sites of DHF and NADPH, and disturb the DHF binding by steric effect, which rarely happens in human DHFR and R24W DHFRL1 mutant.	dihydrofolate	27-30	dihydrofolate reductase 2	Homo sapiens	183-189
24122410-6	2013	The side chain of Arg24 in DHFRL1 can extend deeply into the binding sites of DHF and NADPH, and disturb the DHF binding by steric effect, which rarely happens in human DHFR and R24W DHFRL1 mutant.	dihydrofolate	78-81	dihydrofolate reductase 2	Homo sapiens	27-33
24122410-6	2013	The side chain of Arg24 in DHFRL1 can extend deeply into the binding sites of DHF and NADPH, and disturb the DHF binding by steric effect, which rarely happens in human DHFR and R24W DHFRL1 mutant.	dihydrofolate	78-81	dihydrofolate reductase	Homo sapiens	27-31
24122410-6	2013	The side chain of Arg24 in DHFRL1 can extend deeply into the binding sites of DHF and NADPH, and disturb the DHF binding by steric effect, which rarely happens in human DHFR and R24W DHFRL1 mutant.	dihydrofolate	78-81	dihydrofolate reductase 2	Homo sapiens	183-189
23420416-4	2013	The linkage between protein motions and catalysis is investigated in the context of a model enzyme, E. coli dihydrofolate reductase (DHFR), that catalyzes the hydride transfer reaction in the conversion of dihydrofolate to tetrahydrofolate.	dihydrofolate	108-121	Dihydrofolate reductase	Escherichia coli	133-137
24053355-8	2013	Additional kinetic studies revealed that substrate channeling occurs in which dihydrofolate is directly transferred from the TS to DHFR active site without entering bulk solution.	dihydrofolate	78-91	dihydrofolate reductase	Homo sapiens	131-135
24053355-9	2013	The crystal structure suggests that the positively charged DHFR domain governs this electrostatically mediated movement of dihydrofolate, preventing release from the enzyme.	dihydrofolate	123-136	dihydrofolate reductase	Homo sapiens	59-63
23726796-3	2013	This function maintains the thymidine-5-prime monophosphate pool critical for DNA replication and repair and, THF is generated from dihydrofolate (DHF) through the activity of DHFR.	dihydrofolate	132-145	dihydrofolate reductase	Homo sapiens	176-180
23726796-3	2013	This function maintains the thymidine-5-prime monophosphate pool critical for DNA replication and repair and, THF is generated from dihydrofolate (DHF) through the activity of DHFR.	dihydrofolate	147-150	dihydrofolate reductase	Homo sapiens	176-180
23458706-10	2013	Results from these HHP experiments suggest water release accompanies binding of both the cofactor and DHF to R67 DHFR.	dihydrofolate	102-105	dihydrofolate reductase	Homo sapiens	113-117
23458706-11	2013	In an additional set of experiments, isothermal titration calorimetry studies in H2O and D2O find that water reorganization dominates the enthalpy associated with binding of DHF to R67 DHFR NADP(+), while no obvious effects occur for cofactor binding.	dihydrofolate	174-177	dihydrofolate reductase	Homo sapiens	185-189
23267138-5	2013	Furthermore, DHFR assays in vitro indicated that in the presence of GA, DHFR activity was slightly inhibited and the affinity of the enzyme for dihydrofolate was markedly decreased.	dihydrofolate	144-157	dihydrofolate reductase	Homo sapiens	13-17
22734697-1	2012	On the basis of structural analysis of dihydrofolate reductase (DHFR) (cocrystallized separately with NADPH, dihydrofolate and NADPH, trimethoprim), compounds 2 and 3 were optimized for inhibition of DHFR.	dihydrofolate	39-52	dihydrofolate reductase	Homo sapiens	64-68
22734697-1	2012	On the basis of structural analysis of dihydrofolate reductase (DHFR) (cocrystallized separately with NADPH, dihydrofolate and NADPH, trimethoprim), compounds 2 and 3 were optimized for inhibition of DHFR.	dihydrofolate	39-52	dihydrofolate reductase	Homo sapiens	200-204
22484375-5	2012	The results indicated that MTX induced the depletion of dihydrofolate in melanoma cells, which stimulated the transcriptional activity of E2F1.	dihydrofolate	56-69	metaxin 1	Homo sapiens	27-30
22484375-5	2012	The results indicated that MTX induced the depletion of dihydrofolate in melanoma cells, which stimulated the transcriptional activity of E2F1.	dihydrofolate	56-69	E2F transcription factor 1	Homo sapiens	138-142
20350571-8	2010	Conversely, two phosphinate analogues of 7,8-dihydrofolate that mimic tetrahedral intermediates formed during DHFS- and FPGS-catalysed glutamylation were powerfully inhibitory.	dihydrofolate	41-58	folylpolyglutamate synthase	Homo sapiens	120-124
24300187-1	2012	Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death.	dihydrofolate	98-115	dihydrofolate reductase	Homo sapiens	24-47
24300187-1	2012	Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death.	dihydrofolate	98-115	dihydrofolate reductase	Homo sapiens	49-53
21629435-1	2010	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF).	dihydrofolate	58-71	dihydrofolate reductase	Homo sapiens	0-23
21629435-1	2010	Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF).	dihydrofolate	58-71	dihydrofolate reductase	Homo sapiens	25-29
20795731-1	2010	Plasmid-encoded R67 dihydrofolate reductase (DHFR) catalyzes a hydride transfer reaction between substrate dihydrofolate (DHF) and its cofactor, nicotinamide adenine dinucleotide phosphate (NADPH).	dihydrofolate	20-33	dihydrofolate reductase	Canis lupus familiaris	45-49
20564235-5	2010	First, it acts as a potent antifolate compound, disrupting folate metabolism and increasing intracellular oxidized folate coenzymes, such as dihydrofolate, which is a non-competitive inhibitor of dihydropterine reductase, an enzyme essential for tetrahydrobiopterin (H(4)B) recycling.	dihydrofolate	141-154	H4 clustered histone 4	Homo sapiens	246-272
26596739-6	2012	Subsequently, the method is applied to the dihydrofolate reductase (DHFR) catalyzed reduction of 7,8-dihydrofolate by nicotinamide adenine dinucleotide phosphate hydride (NADPH) to yield S-5,6,7,8-tetrahydrofolate and NADP(+).	dihydrofolate	97-114	dihydrofolate reductase	Homo sapiens	43-66
26596739-6	2012	Subsequently, the method is applied to the dihydrofolate reductase (DHFR) catalyzed reduction of 7,8-dihydrofolate by nicotinamide adenine dinucleotide phosphate hydride (NADPH) to yield S-5,6,7,8-tetrahydrofolate and NADP(+).	dihydrofolate	97-114	dihydrofolate reductase	Homo sapiens	68-72
22369433-2	2012	To explain these unusual results, weak interactions between DHF and osmolytes were proposed, with a competition between osmolyte and DHFR for DHF.	dihydrofolate	60-63	dihydrofolate reductase	Homo sapiens	133-137
21876184-1	2011	Human dihydrofolate reductase (DHFR) was previously thought to be the only enzyme capable of the reduction of dihydrofolate to tetrahydrofolate; an essential reaction necessary to ensure a continuous supply of biologically active folate.	dihydrofolate	6-19	dihydrofolate reductase	Homo sapiens	31-35
21876184-7	2011	The K(m) for NADPH is similar for both enzymes but DHFRL1 has a higher K(m) for dihydrofolate when compared to DHFR.	dihydrofolate	80-93	dihydrofolate reductase 2	Homo sapiens	51-57
21876184-7	2011	The K(m) for NADPH is similar for both enzymes but DHFRL1 has a higher K(m) for dihydrofolate when compared to DHFR.	dihydrofolate	80-93	dihydrofolate reductase	Homo sapiens	51-55
21876184-9	2011	The localization of DHFRL1 to the mitochondria, as demonstrated by confocal microscopy, indicates that mitochondrial dihydrofolate reductase activity may be optimal with a lowered affinity for dihydrofolate.	dihydrofolate	117-130	dihydrofolate reductase 2	Homo sapiens	20-26
19697148-2	2010	Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate that is essential for DNA synthesis.	dihydrofolate	74-87	dihydrofolate reductase	Homo sapiens	25-29
20404044-7	2010	Methotrexate blockage of the AICAR transformylase process in patients with rheumatoid arthritis suggests that dihydrofolate (H(2)folate) reductase is involved and is consistent with H(2)folate and 10-HCO-H(2)folate being the product and substrate for AICAR transformylase.	dihydrofolate	110-123	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	29-34
20404044-7	2010	Methotrexate blockage of the AICAR transformylase process in patients with rheumatoid arthritis suggests that dihydrofolate (H(2)folate) reductase is involved and is consistent with H(2)folate and 10-HCO-H(2)folate being the product and substrate for AICAR transformylase.	dihydrofolate	110-123	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	251-256