PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 24915100-0 2014 Preliminary joint X-ray and neutron protein crystallographic studies of ecDHFR complexed with folate and NADP+. NADP 105-110 dihydrofolate reductase Escherichia coli 72-78 25014833-4 2014 Destabilization of the occluded conformation did not affect hydride transfer but altered the affinity for the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP(+)) and changed the rate-determining step of the catalytic cycle for EcDHFR-S148P. NADP 127-170 dihydrofolate reductase Escherichia coli 246-252 25014833-4 2014 Destabilization of the occluded conformation did not affect hydride transfer but altered the affinity for the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP(+)) and changed the rate-determining step of the catalytic cycle for EcDHFR-S148P. NADP 172-179 dihydrofolate reductase Escherichia coli 246-252 25014833-5 2014 Even in the absence of an occluded conformation, MpDHFR follows a kinetic pathway similar to that of EcDHFR with product release being the rate-limiting step in the steady state at pH 7, suggesting that MpDHFR uses a different strategy to modify its affinity for NADP(+). NADP 263-270 dihydrofolate reductase Escherichia coli 101-107 24915100-4 2014 The neutron and X-ray data were used together for joint refinement of the ecDHFR-folate-NADP+ ternary-complex structure in order to examine the protonation state, protein dynamics and solvent structure of the complex, furthering understanding of the catalytic mechanism. NADP 88-93 dihydrofolate reductase Escherichia coli 74-80 27488762-14 2016 The transcript level of cytosolic NADPH-producing gene involved in folate metabolism is down-regulated by DHFR inhibitors, which highlights the functional significance of DHFR in lipid biosynthesis. NADP 34-39 dihydrofolate reductase Escherichia coli 106-110 27488762-14 2016 The transcript level of cytosolic NADPH-producing gene involved in folate metabolism is down-regulated by DHFR inhibitors, which highlights the functional significance of DHFR in lipid biosynthesis. NADP 34-39 dihydrofolate reductase Escherichia coli 171-175 24915100-1 2014 A crystal of Escherichia coli dihydrofolate reductase (ecDHFR) complexed with folate and NADP+ of 4x1.3x0.7 mm (3.6 mm3) in size was obtained by sequential application of microseeding and macroseeding. NADP 89-94 dihydrofolate reductase Escherichia coli 55-61 22922383-7 2012 This concern has been alleviated via competitive KIE measurements with Escherichia coli dihydrofolate reductase (EcDHFR) that use this specific carbonyl-(14)C NADPH. NADP 159-164 dihydrofolate reductase Escherichia coli 113-119 24152169-6 2013 All phenylalanine derivatives were incorporated with good efficiency into position 16 of ecDHFR and afforded modified proteins that consumed NADPH at rates up to about twice the rate measured for wild type. NADP 141-146 dihydrofolate reductase Escherichia coli 89-95 14503865-1 2003 The interaction of type II R67 dihydrofolate reductase (DHFR) with its cofactor nicotinamide adenine dinucleotide phosphate (NADP(+)) has been studied using nuclear magnetic resonance (NMR). NADP 80-123 dihydrofolate reductase Escherichia coli 56-60 18086667-1 2008 R67 dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate using NADPH as a cofactor. NADP 108-113 dihydrofolate reductase Escherichia coli 29-33 14503865-1 2003 The interaction of type II R67 dihydrofolate reductase (DHFR) with its cofactor nicotinamide adenine dinucleotide phosphate (NADP(+)) has been studied using nuclear magnetic resonance (NMR). NADP 125-132 dihydrofolate reductase Escherichia coli 56-60 14503865-4 2003 The degeneracy of the amide (1)H and (15)N shifts of the tetrameric DHFR was preserved upon addition of NADP(+), consistent with kinetic averaging among equivalent binding sites. NADP 104-108 dihydrofolate reductase Escherichia coli 68-72 14503865-5 2003 Analysis of the more titration-sensitive DHFR amide resonances as a function of added NADP(+) gave a K(D) of 131 +/- 50 microM, consistent with previous determinations using other methodology. NADP 86-90 dihydrofolate reductase Escherichia coli 41-45 14503865-6 2003 We have found that the (1)H spectrum of NADP(+) in the presence of the R67 DHFR changes as a function of time. NADP 40-44 dihydrofolate reductase Escherichia coli 75-79 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. NADP 99-104 dihydrofolate reductase Escherichia coli 131-135 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. NADP 213-218 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. NADP 77-81 dihydrofolate reductase Escherichia coli 140-144 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. NADP 145-150 dihydrofolate reductase Escherichia coli 140-144 1426244-6 1992 Addition of either NADP+ or NADPH to the E. coli DHFR-MTX complex results in a single set of 13C signals for bound methotrexate consistent with only one conformational form in the ternary complexes. NADP 19-24 dihydrofolate reductase Escherichia coli 49-53 9012674-12 1997 Loop movement, also unobserved in vertebrate DHFR structures, may preferentially weaken NADP+ vs NADPH binding in ecDHFR, an evolutionary adaptation to reduce product inhibition in the NADP+ rich environment of prokaryotes. NADP 88-93 dihydrofolate reductase Escherichia coli 45-49 9012674-12 1997 Loop movement, also unobserved in vertebrate DHFR structures, may preferentially weaken NADP+ vs NADPH binding in ecDHFR, an evolutionary adaptation to reduce product inhibition in the NADP+ rich environment of prokaryotes. NADP 88-93 dihydrofolate reductase Escherichia coli 114-120 9012674-12 1997 Loop movement, also unobserved in vertebrate DHFR structures, may preferentially weaken NADP+ vs NADPH binding in ecDHFR, an evolutionary adaptation to reduce product inhibition in the NADP+ rich environment of prokaryotes. NADP 97-102 dihydrofolate reductase Escherichia coli 45-49 9012674-12 1997 Loop movement, also unobserved in vertebrate DHFR structures, may preferentially weaken NADP+ vs NADPH binding in ecDHFR, an evolutionary adaptation to reduce product inhibition in the NADP+ rich environment of prokaryotes. NADP 97-102 dihydrofolate reductase Escherichia coli 114-120 9012674-12 1997 Loop movement, also unobserved in vertebrate DHFR structures, may preferentially weaken NADP+ vs NADPH binding in ecDHFR, an evolutionary adaptation to reduce product inhibition in the NADP+ rich environment of prokaryotes. NADP 185-190 dihydrofolate reductase Escherichia coli 45-49 9012674-12 1997 Loop movement, also unobserved in vertebrate DHFR structures, may preferentially weaken NADP+ vs NADPH binding in ecDHFR, an evolutionary adaptation to reduce product inhibition in the NADP+ rich environment of prokaryotes. NADP 185-190 dihydrofolate reductase Escherichia coli 114-120 7873554-10 1995 When the ecDHFR.NADPH complex (space group P3221; M. R. Sawaya, in preparation) is superimposed on the folate and 5dfol complexes, the distances from pteridine C6 to nicotinamide C4 were found to be 2.9 and 2.8 A, respectively, in close agreement with the theoretically calculated optimal distance in the transition state for hydride transfer [Wu, Y. D., & Houk, K. N. (1987) J. NADP 16-21 dihydrofolate reductase Escherichia coli 9-15 9012674-1 1997 The reaction catalyzed by Escherichia coli dihydrofolate reductase (ecDHFR) cycles through five detectable kinetic intermediates: holoenzyme, Michaelis complex, ternary product complex, tetrahydrofolate (THF) binary complex, and THF.NADPH complex. NADP 233-238 dihydrofolate reductase Escherichia coli 68-74 1426244-6 1992 Addition of either NADP+ or NADPH to the E. coli DHFR-MTX complex results in a single set of 13C signals for bound methotrexate consistent with only one conformational form in the ternary complexes. NADP 28-33 dihydrofolate reductase Escherichia coli 49-53 1915851-5 1991 In contrast, only one conformation was observed for both the DHFR/folate and DHFR/folate/NADP+ complexes. NADP 89-94 dihydrofolate reductase Escherichia coli 77-81 30198899-1 2018 A high-pressure crystallographic study was conducted on Escherichia coli dihydrofolate reductase (ecDHFR) complexed with folate and NADP+ in crystal forms containing both the open and closed conformations of the M20 loop under high-pressure conditions of up to 800 MPa. NADP 132-137 dihydrofolate reductase Escherichia coli 98-104 2108144-4 1990 The equilibrium proportion of Et in the absence of ligands is 63%, but binding of NADPH greatly increases this proportion, and t1/2 for conversion of Ew.NADPH to Et.NADPH is 30 s. This conformational equilibrium has also been examined in mutant enzyme in which aspartate 27 is replaced by asparagine (D27N E. coli DHFR). NADP 82-87 dihydrofolate reductase Escherichia coli 314-318 2108144-4 1990 The equilibrium proportion of Et in the absence of ligands is 63%, but binding of NADPH greatly increases this proportion, and t1/2 for conversion of Ew.NADPH to Et.NADPH is 30 s. This conformational equilibrium has also been examined in mutant enzyme in which aspartate 27 is replaced by asparagine (D27N E. coli DHFR). NADP 153-158 dihydrofolate reductase Escherichia coli 314-318 2108144-4 1990 The equilibrium proportion of Et in the absence of ligands is 63%, but binding of NADPH greatly increases this proportion, and t1/2 for conversion of Ew.NADPH to Et.NADPH is 30 s. This conformational equilibrium has also been examined in mutant enzyme in which aspartate 27 is replaced by asparagine (D27N E. coli DHFR). NADP 153-158 dihydrofolate reductase Escherichia coli 314-318 2108144-6 1990 However, for mutant apoenzyme, the proportion of Et is decreased to 18% in the absence of ligands so that the overall KD for NADPH is increased (0.15 microM for WT E. coli DHFR, 0.68 microM for D27N E. coli DHFR). NADP 125-130 dihydrofolate reductase Escherichia coli 172-176 2108144-6 1990 However, for mutant apoenzyme, the proportion of Et is decreased to 18% in the absence of ligands so that the overall KD for NADPH is increased (0.15 microM for WT E. coli DHFR, 0.68 microM for D27N E. coli DHFR). NADP 125-130 dihydrofolate reductase Escherichia coli 207-211 1758881-3 1991 Further calculations on proposed enzyme mutants show that the polarization of NADPH on binding to DHFR is, in large part, induced by a motif of three positively charged residues. NADP 78-83 dihydrofolate reductase Escherichia coli 98-102 1758881-5 1991 The possibility of this long-range polarization of NADPH was originally proposed based on a previous study of ligand binding to DHFR where a conserved structural motif of three positively charged residues was found to play a major role in polarizing the substrate folate over its entire length of 18 A. NADP 51-56 dihydrofolate reductase Escherichia coli 128-132 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). NADP 146-151 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). NADP 146-151 dihydrofolate reductase Escherichia coli 260-264 30198899-3 2018 Several structural changes in ecDHFR were observed at high pressure that were also accompanied by structural changes in the NADP+ cofactor and the hydration structure. NADP 124-129 dihydrofolate reductase Escherichia coli 30-36