dihydrofolate reductase

Summary

Gene Symbol: dihydrofolate reductase
Description: dihydrofolate reductase
Alias: DHFRP1, DYR, dihydrofolate reductase
Species: human
Products:     dihydrofolate reductase

Top Publications

  1. Davies J, Delcamp T, Prendergast N, Ashford V, Freisheim J, Kraut J. Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate. Biochemistry. 1990;29:9467-79 pubmed
    The 2.3-A crystal structure of recombinant human dihydrofolate reductase (EC 1.5.1.3, DHFR) has been solved as a binary complex with folate (a poor substrate at neutral pH) and also as a binary complex with an inhibitor, 5-deazafolate...
  2. Parle McDermott A, Pangilinan F, Mills J, Kirke P, Gibney E, Troendle J, et al. The 19-bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR) may decrease rather than increase risk for spina bifida in the Irish population. Am J Med Genet A. 2007;143A:1174-80 pubmed
    ..This has focused attention on folate-related genes such as dihydrofolate reductase (DHFR) in a bid to identify the genetic factors that influence NTD risk through either the fetal or ..
  3. Bhabha G, Tuttle L, Martinez Yamout M, Wright P. Identification of endogenous ligands bound to bacterially expressed human and E. coli dihydrofolate reductase by 2D NMR. FEBS Lett. 2011;585:3528-32 pubmed publisher
    b>Dihydrofolate reductase (DHFR) is a well-studied drug target and a paradigm for understanding enzyme catalysis...
  4. Liu C, Hanoian P, French J, Pringle T, Hammes Schiffer S, Benkovic S. Functional significance of evolving protein sequence in dihydrofolate reductase from bacteria to humans. Proc Natl Acad Sci U S A. 2013;110:10159-64 pubmed publisher
    ..Here we trace the evolution of dihydrofolate reductase (DHFR) and identify multiple key divergence sites among 233 species between humans and bacteria...
  5. Johnson W, Stenroos E, Spychala J, Chatkupt S, Ming S, Buyske S. New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR): a risk factor for spina bifida acting in mothers during pregnancy?. Am J Med Genet A. 2004;124A:339-45 pubmed
    ..We recently discovered a polymorphic 19 bp deletion allele (frequency 0.45) within intron-1 of dihydrofolate reductase (DHFR) that is a good candidate for such a genetic factor...
  6. Bhabha G, Ekiert D, Jennewein M, Zmasek C, Tuttle L, Kroon G, et al. Divergent evolution of protein conformational dynamics in dihydrofolate reductase. Nat Struct Mol Biol. 2013;20:1243-9 pubmed publisher
    ..We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family...
  7. Chen M, Shimada T, Moulton A, Cline A, Humphries R, Maizel J, et al. The functional human dihydrofolate reductase gene. J Biol Chem. 1984;259:3933-43 pubmed
    ..cloning, mapping, and DNA sequencing techniques have been used to characterize the functional human dihydrofolate reductase (DHFR) gene. The gene is about 30 kilobases in length...
  8. Matherly L, Taub J, Wong S, Simpson P, Ekizian R, Buck S, et al. Increased frequency of expression of elevated dihydrofolate reductase in T-cell versus B-precursor acute lymphoblastic leukemia in children. Blood. 1997;90:578-89 pubmed
    The relationships between dihydrofolate reductase (DHFR) levels or methotrexate membrane transport and acute lymphoblastic leukemia (ALL) immunophenotype were evaluated on 51 T-cell and 44 B-precursor ALL specimens from 90 pediatric ALL ..
  9. Leveson Gower D, Michnick S, Ling V. Detection of TAP family dimerizations by an in vivo assay in mammalian cells. Biochemistry. 2004;43:14257-64 pubmed
    ..To identify interactions within the human TAP family, we adapted the dihydrofolate reductase protein-fragment complementation assay (DHFR PCA) to half ABC transporters...
  10. Summers C, Mitchell L, Stanislawska Sachadyn A, Baido S, Blair I, Von Feldt J, et al. Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women. Birth Defects Res A Clin Mol Teratol. 2010;88:679-88 pubmed publisher
    ..In African American and Caucasian women, different factors are associated with folate/Hcy phenotypes and may contribute to race-specific differences in the risks of a range of pregnancy-related pathologies. ..

Detail Information

Publications62

  1. Davies J, Delcamp T, Prendergast N, Ashford V, Freisheim J, Kraut J. Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate. Biochemistry. 1990;29:9467-79 pubmed
    The 2.3-A crystal structure of recombinant human dihydrofolate reductase (EC 1.5.1.3, DHFR) has been solved as a binary complex with folate (a poor substrate at neutral pH) and also as a binary complex with an inhibitor, 5-deazafolate...
  2. Parle McDermott A, Pangilinan F, Mills J, Kirke P, Gibney E, Troendle J, et al. The 19-bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR) may decrease rather than increase risk for spina bifida in the Irish population. Am J Med Genet A. 2007;143A:1174-80 pubmed
    ..This has focused attention on folate-related genes such as dihydrofolate reductase (DHFR) in a bid to identify the genetic factors that influence NTD risk through either the fetal or ..
  3. Bhabha G, Tuttle L, Martinez Yamout M, Wright P. Identification of endogenous ligands bound to bacterially expressed human and E. coli dihydrofolate reductase by 2D NMR. FEBS Lett. 2011;585:3528-32 pubmed publisher
    b>Dihydrofolate reductase (DHFR) is a well-studied drug target and a paradigm for understanding enzyme catalysis...
  4. Liu C, Hanoian P, French J, Pringle T, Hammes Schiffer S, Benkovic S. Functional significance of evolving protein sequence in dihydrofolate reductase from bacteria to humans. Proc Natl Acad Sci U S A. 2013;110:10159-64 pubmed publisher
    ..Here we trace the evolution of dihydrofolate reductase (DHFR) and identify multiple key divergence sites among 233 species between humans and bacteria...
  5. Johnson W, Stenroos E, Spychala J, Chatkupt S, Ming S, Buyske S. New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR): a risk factor for spina bifida acting in mothers during pregnancy?. Am J Med Genet A. 2004;124A:339-45 pubmed
    ..We recently discovered a polymorphic 19 bp deletion allele (frequency 0.45) within intron-1 of dihydrofolate reductase (DHFR) that is a good candidate for such a genetic factor...
  6. Bhabha G, Ekiert D, Jennewein M, Zmasek C, Tuttle L, Kroon G, et al. Divergent evolution of protein conformational dynamics in dihydrofolate reductase. Nat Struct Mol Biol. 2013;20:1243-9 pubmed publisher
    ..We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family...
  7. Chen M, Shimada T, Moulton A, Cline A, Humphries R, Maizel J, et al. The functional human dihydrofolate reductase gene. J Biol Chem. 1984;259:3933-43 pubmed
    ..cloning, mapping, and DNA sequencing techniques have been used to characterize the functional human dihydrofolate reductase (DHFR) gene. The gene is about 30 kilobases in length...
  8. Matherly L, Taub J, Wong S, Simpson P, Ekizian R, Buck S, et al. Increased frequency of expression of elevated dihydrofolate reductase in T-cell versus B-precursor acute lymphoblastic leukemia in children. Blood. 1997;90:578-89 pubmed
    The relationships between dihydrofolate reductase (DHFR) levels or methotrexate membrane transport and acute lymphoblastic leukemia (ALL) immunophenotype were evaluated on 51 T-cell and 44 B-precursor ALL specimens from 90 pediatric ALL ..
  9. Leveson Gower D, Michnick S, Ling V. Detection of TAP family dimerizations by an in vivo assay in mammalian cells. Biochemistry. 2004;43:14257-64 pubmed
    ..To identify interactions within the human TAP family, we adapted the dihydrofolate reductase protein-fragment complementation assay (DHFR PCA) to half ABC transporters...
  10. Summers C, Mitchell L, Stanislawska Sachadyn A, Baido S, Blair I, Von Feldt J, et al. Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women. Birth Defects Res A Clin Mol Teratol. 2010;88:679-88 pubmed publisher
    ..In African American and Caucasian women, different factors are associated with folate/Hcy phenotypes and may contribute to race-specific differences in the risks of a range of pregnancy-related pathologies. ..
  11. Semmler A, Bao X, Cao G, Kohler W, Weller M, Aubourg P, et al. Genetic variants of methionine metabolism and X-ALD phenotype generation: results of a new study sample. J Neurol. 2009;256:1277-80 pubmed publisher
    ..Whereas the influence of other polymorphisms of methionine metabolism was not confirmed, the present study supports the previously made observation that the Tc2 genotype contributes to X-ALD phenotype generation. ..
  12. Zhou C, Zhu X, Elsheikha H, He S, Li Q, Zhou D, et al. Global iTRAQ-based proteomic profiling of Toxoplasma gondii oocysts during sporulation. J Proteomics. 2016;148:12-9 pubmed publisher
    ..ACL), GMP synthase, IMP dehydrogenase (IMPDH), poly (ADP-ribose) glycohydrolase (PARG), and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) as the top five hubs...
  13. Wang Y, Ha S, Zhang T, Kho D, Raz A, Xie Y. Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases. Oncotarget. 2014;5:2044-51 pubmed publisher
    ..This study uncovers a previously unknown functional link between gp78 and TRIM25 and provides mechanistic insight into gp78-mediated protein ubiquitylation...
  14. Chao B, Li B, Xiao X. Design, synthesis and evaluation of antitumor acylated monoaminopyrroloquinazolines. Bioorg Med Chem Lett. 2017;27:3107-3110 pubmed publisher
    ..N-1 primary amino group in 1,3-diaminopyrroloquinazoline is critical for its inhibitory activity against dihydrofolate reductase (DHFR)...
  15. Marverti G, Ligabue A, Lombardi P, Ferrari S, Monti M, Frassineti C, et al. Modulation of the expression of folate cycle enzymes and polyamine metabolism by berberine in cisplatin-sensitive and -resistant human ovarian cancer cells. Int J Oncol. 2013;43:1269-80 pubmed publisher
    ..cells more than the sensitive counterparts, by interfering with the expression of folate cycle enzymes, dihydrofolate reductase (DHFR) and thymidylate synthase (TS)...
  16. Beltzer J, Spiess M. In vitro binding of the asialoglycoprotein receptor to the beta adaptin of plasma membrane coated vesicles. EMBO J. 1991;10:3735-42 pubmed
    ..The cytoplasmic domain of the ASGP receptor subunit H1 fused to dihydrofolate reductase competed for receptor binding to the 100 kDa polypeptide in the plasma membrane-type AP complexes (AP-2)...
  17. Patel P, Bharti P, Bansal D, Ali N, Raman R, Mohapatra P, et al. Prevalence of mutations linked to antimalarial resistance in Plasmodium falciparum from Chhattisgarh, Central India: A malaria elimination point of view. Sci Rep. 2017;7:16690 pubmed publisher
    ..These findings provide potential information and understanding of the evolution and spread of different drug resistance alleles in Chhattisgarh. ..
  18. Porter K, Basu A, Hubbard A, Bates M, Kalman D, Rey O, et al. Association of genetic variation in cystathionine-beta-synthase and arsenic metabolism. Environ Res. 2010;110:580-7 pubmed publisher
    ..MTHFR), methionine synthase (MTR), cystathionine-beta-synthase (CBS), thymidylate synthase (TYMS), dihydrofolate reductase (DHFR), serine hydroxymethyltransferase 1 (SHMT1)] and glutathione biosynthesis [glutathione-S-..
  19. Ng X, Boyd L, Dufficy L, Naumovski N, Blades B, Travers C, et al. Folate nutritional genetics and risk for hypertension in an elderly population sample. J Nutrigenet Nutrigenomics. 2009;2:1-8 pubmed publisher
    ..Regressing diastolic blood pressure and 677C>T-MTHFR genotype showed significance (males; p = 0.032) and borderline significance (all subjects). Dietary folate and 677C>T-MTHFR genotype may modify blood pressure. ..
  20. Toma H, Imada Y, Vannachone B, Miyagi M, Kobayashi J, Uechi G, et al. A molecular epidemiologic study of point mutations for pyrimethamine-sulfadoxine resistance of Plasmodium falciparum isolates from Lao PDR. Southeast Asian J Trop Med Public Health. 2005;36:602-4 pubmed
    ..PS) resistant falciparum malaria in Lao PDR, the frequency of point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum were examined in 50 blood ..
  21. Stanisławska Sachadyn A, Brown K, Mitchell L, Woodside J, Young I, Scott J, et al. An insertion/deletion polymorphism of the dihydrofolate reductase (DHFR) gene is associated with serum and red blood cell folate concentrations in women. Hum Genet. 2008;123:289-95 pubmed publisher
    ..b>Dihydrofolate reductase catalyzes the reduction of folic acid to dihydrofolate and thereafter to tetrahydrofolate...
  22. Masterson J, Schwartz S. Evolution alters the enzymatic reaction coordinate of dihydrofolate reductase. J Phys Chem B. 2015;119:989-96 pubmed publisher
    ..Evolutionary changes from Escherichia coli dihydrofolate reductase (ecDHFR) to human dihydrofolate reductase (hsDHFR) have resulted in increased catalytic efficiency and an ..
  23. Lee S, Chen T, Lin L, Li C, Chen L, Hsing C, et al. Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma. Exp Mol Pathol. 2013;95:83-90 pubmed publisher
    Data mining on public domain identified that thymidylate synthetase (TYMS) and dihydrofolate reductase (DHFR) transcripts were significantly higher expressed in nasopharyngeal carcinoma (NPC)...
  24. Craciun G, Tang Y, Feinberg M. Understanding bistability in complex enzyme-driven reaction networks. Proc Natl Acad Sci U S A. 2006;103:8697-702 pubmed
    ..Moreover, we indicate how switch-like behavior results from a well-studied mechanism for the action of human dihydrofolate reductase, an important anti-cancer target.
  25. Dutta S, Shaw J, Chatterjee A, Sarkar K, Usha R, Chatterjee A, et al. Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability. Nutr Neurosci. 2011;14:202-9 pubmed publisher
    ..002). A strong correlation between rs1801394 'G' allele and micronucleus was also noticed. From the present investigation, a role of genetic polymorphisms and vitamin B6 levels could be hypothesized in the etiology of IID. ..
  26. Park K, Rue S, Lee I, Kim H, Lee I, Ahn J, et al. Modulation of Sp1-dependent transcription by a cis-acting E2F element in dhfr promoter. Biochem Biophys Res Commun. 2003;306:239-43 pubmed
    The dihydrofolate reductase (dhfr) promoter contains cis-acting elements for Sp1 and E2F. Here we examined the cooperative regulation of dhfr gene transcription by Sp1 and E2F in human osteosarcoma cells, U2OS...
  27. Cario H, Smith D, Blom H, Blau N, Bode H, Holzmann K, et al. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. Am J Hum Genet. 2011;88:226-31 pubmed publisher
    ..Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p...
  28. Salazar J, Moya P, Altes A, Diaz Torne C, Casademont J, Cerdá Gabaroi D, et al. Polymorphisms in genes involved in the mechanism of action of methotrexate: are they associated with outcome in rheumatoid arthritis patients?. Pharmacogenomics. 2014;15:1079-90 pubmed publisher
    ..026). The ATIC rs16853826 variant was associated with toxicity (p = 0.039). MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy. ..
  29. Cam R, Eroglu A, Egin Y, Akar N. Dihydrofolate reductase (DHRF) 19-bp intron-1 deletion and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms in breast cancer. Breast Cancer Res Treat. 2009;115:431-2 pubmed publisher
  30. Hughes R, Johnson L, Behiry E, Loveridge E, Allemann R. A Rapid Analysis of Variations in Conformational Behavior during Dihydrofolate Reductase Catalysis. Biochemistry. 2017;56:2126-2133 pubmed publisher
    ..Here a generic and rapid procedure for identifying conformational changes during dihydrofolate reductase (DHFR) catalysis is described...
  31. Yuan T, Huang Y, Zhou C, Yu Y, Wang L, Zhuang H, et al. Nuclear translocation of dihydrofolate reductase is not a pre-requisite for DNA damage induced apoptosis. Apoptosis. 2009;14:699-710 pubmed publisher
    b>Dihydrofolate reductase (DHFR) is a key enzyme for the synthesis of thymidylate, and therefore, of DNA...
  32. Vanguri V, Wang S, Godyna S, Ranganathan S, Liau G. Thrombospondin-1 binds to polyhistidine with high affinity and specificity. Biochem J. 2000;347:469-73 pubmed
    ..The possibility that other polyhistidine-containing proteins also interact with TSP1 warrants further study. ..
  33. Thapliyal C, Jain N, Rashid N, Chaudhuri Chattopadhyay P. Kinetics and thermodynamics of the thermal inactivation and chaperone assisted folding of zebrafish dihydrofolate reductase. Arch Biochem Biophys. 2018;637:21-30 pubmed publisher
    ....
  34. Semmler A, Linnebank M, Krex D, Götz A, Moskau S, Ziegler A, et al. Polymorphisms of homocysteine metabolism are associated with intracranial aneurysms. Cerebrovasc Dis. 2008;26:425-9 pubmed publisher
    ..677C-->T, MTHFR c.1298A-->C, cystathionine beta-synthase (CBS) c.844_855ins68, CBS c.833T-->C, dihydrofolate reductase (DHFR) c.594 + 59del19bp, glutathione S-transferase Omega-1 (GSTO1) c...
  35. Wang Y, Ragavan M, Hilty C. Site specific polarization transfer from a hyperpolarized ligand of dihydrofolate reductase. J Biomol NMR. 2016;65:41-8 pubmed publisher
    ..Here, folic acid, a ligand of dihydrofolate reductase (DHFR), was hyperpolarized on (1)H spins using dissolution dynamic nuclear polarization (D-DNP)...
  36. Masters J, Yang J, Cellini A, Attardi G. A human dihydrofolate reductase pseudogene and its relationship to the multiple forms of specific messenger RNA. J Mol Biol. 1983;167:23-36 pubmed
    The presence of dihydrofolate reductase (DHFRase)-specific sequences that, in contrast to the normal DHFRase gene, are not amplified in a methotrexate-resistant cell line, has been detected in the DNA from human sperm and from several ..
  37. Zhang K, Rathod P. Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science. 2002;296:545-7 pubmed
    ..against Plasmodium falciparum malaria has been attributed to host-parasite differences in drug binding to dihydrofolate reductase-thymidylate synthase (DHFR-TS)...
  38. Martinelli M, Girardi A, Cura F, Carinci F, Morselli P, Scapoli L. Evidence of the involvement of the DHFR gene in nonsyndromic cleft lip with or without cleft palate. Eur J Med Genet. 2014;57:1-4 pubmed publisher
    ..In this article, we considered the dihydrofolate reductase (DHFR) gene, previously seen implicated in NTDs, as a candidate for cleft lip with or without cleft ..
  39. Mehrotra E, Vishwakarma J, Tripathi A, Sonar P, Saraf S. Schizonticidal antimalarial sesquiterpene lactones from Magnolia champaca (L.) Baill. ex Pierre: microwave-assisted extraction, HPTLC fingerprinting and computational studies. Nat Prod Res. 2017;:1-5 pubmed publisher
    ..Additionally, favourable in silico ADMET parameters were envisaged through various computational programmes...
  40. Kalmbach R, Choumenkovitch S, Troen A, Jacques P, D AGOSTINO R, Selhub J. A 19-base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate. J Nutr. 2008;138:2323-7 pubmed publisher
    b>Dihydrofolate reductase (DHFR) catalyzes the reduction of folic acid to tetrahydrofolate (THF)...
  41. Martinelli A, Henriques G, Cravo P, Hunt P. Whole genome re-sequencing identifies a mutation in an ABC transporter (mdr2) in a Plasmodium chabaudi clone with altered susceptibility to antifolate drugs. Int J Parasitol. 2011;41:165-71 pubmed publisher
    In malaria parasites, mutations in two genes of folate biosynthesis encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) modify responses to antifolate therapies which target these enzymes...
  42. Hayashi H, Horino M, Morishita M, Tazoe Y, Tsuboi S, Matsuyama T, et al. Dihydrofolate reductase gene intronic 19-bp deletion polymorphisms in a Japanese population. Drug Metab Pharmacokinet. 2010;25:516-8 pubmed
    b>Dihydrofolate reductase gene (DHFR) 19-bp deletion polymorphisms result in varied DHFR enzymatic activity affecting the risk for preterm delivery, spina bifida, and the efficacy of methotrexate (MTX)...
  43. Summers C, Cucchiara A, Nackos E, Hammons A, Mohr E, Whitehead A, et al. Functional polymorphisms of folate-metabolizing enzymes in relation to homocysteine concentrations in systemic lupus erythematosus. J Rheumatol. 2008;35:2179-86 pubmed
    ..2756A>G, methionine synthase reductase (MTRR) 66A>G, thymidylate synthase (TYMS) 1494del6, and dihydrofolate reductase (DHFR) c.86+60_78...
  44. Bailey S, Ayling J. The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Proc Natl Acad Sci U S A. 2009;106:15424-9 pubmed publisher
    ..not significantly found in fresh natural foods; to be used it must be converted to tetrahydrofolate by dihydrofolate reductase (DHFR). Increasing evidence suggests that this process may be slow in humans...
  45. Kumar M, Kaur T, Sharma A. Role of computational efficiency indices and pose clustering in effective decision making: An example of annulated furanones in Pf-DHFR space. Comput Biol Chem. 2017;67:48-61 pubmed publisher
    ..These kind of guidelines can help medicinal chemists in prioritization their work and in effective management of time, energy and chemical resources. ..
  46. Meyer K, Fredriksen A, Ueland P. MALDI-TOF MS genotyping of polymorphisms related to 1-carbon metabolism using common and mass-modified terminators. Clin Chem. 2009;55:139-49 pubmed publisher
    ..This was demonstrated with 20 polymorphisms involved in 1-carbon metabolism. ..
  47. Linn A, Samainukul N, Sakdee S, Angsuthanasombat C, Katzenmeier G. A Helicobacter pylori Vacuolating Cytotoxin A: Mouse DHFR Fusion Protein Triggers Dye Release from Liposomes. Curr Microbiol. 2017;: pubmed publisher
    ..Our findings suggest that the VacA p88 toxin with a modified N-terminus still maintains its capability for membrane insertion and that pH-dependent conformational changes occur during interaction of VacA with membranes...
  48. Panecka Hofman J, Pöhner I, Spyrakis F, Zeppelin T, Di Pisa F, Dello Iacono L, et al. Comparative mapping of on-targets and off-targets for the discovery of anti-trypanosomatid folate pathway inhibitors. Biochim Biophys Acta. 2017;1861:3215-3230 pubmed publisher
    ..i) the primary parasite on-targets: pteridine reductase 1 (PTR1) (absent in humans) and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), (ii) the primary off-targets: human DHFR and TS, and (iii) the secondary ..
  49. Paniz C, Bertinato J, Lucena M, De Carli E, Amorim P, Gomes G, et al. A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults. J Nutr. 2017;147:1677-1685 pubmed publisher
    ..5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon γ (IFNG), tumor ..
  50. El Gazzar Y, Georgey H, El Messery S, Ewida H, Hassan G, Raafat M, et al. Synthesis, biological evaluation and molecular modeling study of new (1,2,4-triazole or 1,3,4-thiadiazole)-methylthio-derivatives of quinazolin-4(3H)-one as DHFR inhibitors. Bioorg Chem. 2017;72:282-292 pubmed publisher
    ..Compound 17 shared a similar molecular docking mode with MTX and made a critical hydrogen bond and arene-arene interactions via Ala9 and Phe34 amino acid residues, respectively. ..
  51. Lenz B, Soehngen C, Linnebank M, Heberlein A, Frieling H, Kornhuber J, et al. Genetic polymorphisms relevant for one-carbon metabolism show no effect on homocysteine plasma levels and DNA methylation in alcoholism. Psychiatr Genet. 2009;19:215-6 pubmed publisher
  52. Eskandari Nasab E, Hashemi M, Rezaei H, Fazaeli A, Mashhadi M, Moghaddam S, et al. Evaluation of UDP-glucuronosyltransferase 2B17 (UGT2B17) and dihydrofolate reductase (DHFR) genes deletion and the expression level of NGX6 mRNA in breast cancer. Mol Biol Rep. 2012;39:10531-9 pubmed publisher
    ..Furthermore, down-regulation of NGX6 mRNA expression in breast carcinoma confirms the growing proof regarding the tumor suppressor role of NGX6. ..
  53. Maguire M, Nield P, Devling T, Jenkins R, Park B, Polański R, et al. MDM2 regulates dihydrofolate reductase activity through monoubiquitination. Cancer Res. 2008;68:3232-42 pubmed publisher
    ..Here, we describe the identification of a novel substrate for the MDM2 ubiquitin ligase: dihydrofolate reductase (DHFR). MDM2 binds directly to DHFR and catalyses its monoubiquitination and not its polyubiquitination...
  54. Rushworth D, Mathews A, Alpert A, Cooper L. Dihydrofolate Reductase and Thymidylate Synthase Transgenes Resistant to Methotrexate Interact to Permit Novel Transgene Regulation. J Biol Chem. 2015;290:22970-6 pubmed publisher
    ..MTX inhibits thymidine synthesis by targeting dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS)...
  55. Levine A, Figueiredo J, Lee W, Conti D, Kennedy K, Duggan D, et al. A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2010;19:1812-21 pubmed publisher
    ..This study suggests that multivitamin supplement use may modify the association between folate pathway genes and colorectal cancer risk in a post-folic-acid-supplemented population. ..
  56. Malisa A, Pearce R, Abdullah S, Mutayoba B, Mshinda H, Kachur P, et al. Molecular monitoring of resistant dhfr and dhps allelic haplotypes in Morogoro and Mvomero districts in south eastern Tanzania. Afr Health Sci. 2011;11:142-50 pubmed
    ....
  57. Martianov I, Ramadass A, Serra Barros A, Chow N, Akoulitchev A. Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature. 2007;445:666-70 pubmed
    ..in quiescent cells the mechanism of transcriptional repression of the major promoter of the gene encoding dihydrofolate reductase depends on a non-coding transcript initiated from the upstream minor promoter and involves both the ..
  58. Nakano M, Fukami T, Gotoh S, Nakajima M. A-to-I RNA Editing Up-regulates Human Dihydrofolate Reductase in Breast Cancer. J Biol Chem. 2017;292:4873-4884 pubmed publisher
    b>Dihydrofolate reductase (DHFR) plays a key role in folate metabolism and is a target molecule of methotrexate. An increase in the cellular expression level of DHFR is one of the mechanisms of tumor resistance to methotrexate...
  59. Choi J, Yates Z, Martin C, Boyd L, Ng X, Skinner V, et al. Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report. J Nutr Sci Vitaminol (Tokyo). 2015;61:455-9 pubmed publisher
    Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to ..
  60. Okell L, Griffin J, Roper C. Mapping sulphadoxine-pyrimethamine-resistant Plasmodium falciparum malaria in infected humans and in parasite populations in Africa. Sci Rep. 2017;7:7389 pubmed publisher
    ..We propose that the use of resistance frequencies as well as prevalence measures for policy decisions should be evaluated. ..
  61. Banerjee D, Mayer Kuckuk P, Capiaux G, Budak Alpdogan T, Gorlick R, Bertino J. Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochim Biophys Acta. 2002;1587:164-73 pubmed
    ..to the thymidylate biosynthesis pathway especially those that target thymidylate synthase (TS) and dihydrofolate reductase (DHFR)...
  62. Stevens V, Rodriguez C, Sun J, Talbot J, Thun M, Calle E. No association of single nucleotide polymorphisms in one-carbon metabolism genes with prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:3612-4 pubmed publisher
    ..Thus, our findings do not support the hypothesis that common genetic variation in one-carbon metabolism genes influences prostate cancer risk. ..