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Chemical Compound Review

SureCN8281     2-[[4-[(2-amino-4-oxo-7,8- dihydro-1H...

Synonyms: SureCN2510798, NSC-165989, AC1Q5SFR, NSC165989, AR-1J8789, ...
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Disease relevance of dihydrofolate


High impact information on dihydrofolate


Chemical compound and disease context of dihydrofolate


Biological context of dihydrofolate


Anatomical context of dihydrofolate


Associations of dihydrofolate with other chemical compounds

  • Substrate (dihydrofolate) and cofactor (NADPH) binding is also diminished for the mutant enzyme, although to a lesser extent (17.3- and 3.6-fold higher Km, respectively) [26].
  • In this paper, we report the use of 1H and 13C NMR spectroscopy to study the fluctuations in conformation of the anti-bacterial drug trimethoprim when it is bound to its "target," dihydrofolate reductase [27].
  • Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana [22].
  • Pyrimethamine (Pyr) targets dihydrofolate reductase of Plasmodium vivax (PvDHFR) as well as other malarial parasites, but its use as antimalarial is hampered by the widespread high resistance [28].
  • The total stabilization by leucine-54 of the transition state for hydride transfer is ca. 10(4)-fold (delta delta G approximately 5.4 kcal/mol) at subsaturating dihydrofolate levels relative to free enzyme despite its location some 10 A from the site of chemical reaction [29].

Gene context of dihydrofolate


Analytical, diagnostic and therapeutic context of dihydrofolate


  1. Metaphase chromosome anomaly: association with drug resistance and cell-specific products. Biedler, J.L., Spengler, B.A. Science (1976) [Pubmed]
  2. FamClash: a method for ranking the activity of engineered enzymes. Saraf, M.C., Horswill, A.R., Benkovic, S.J., Maranas, C.D. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells. Rice, G.C., Hoy, C., Schimke, R.T. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  4. Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Peterson, D.S., Walliker, D., Wellems, T.E. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  5. Phenotypic expression in Escherichia coli and nucleotide sequence of two Chinese hamster lung cell cDNAs encoding different dihydrofolate reductases. Melera, P.W., Davide, J.P., Hession, C.A., Scotto, K.W. Mol. Cell. Biol. (1984) [Pubmed]
  6. Identification of an origin of bidirectional DNA replication in mammalian chromosomes. Burhans, W.C., Vassilev, L.T., Caddle, M.S., Heintz, N.H., DePamphilis, M.L. Cell (1990) [Pubmed]
  7. DNA repair in an active gene: removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall. Bohr, V.A., Smith, C.A., Okumoto, D.S., Hanawalt, P.C. Cell (1985) [Pubmed]
  8. Deletion of the diploid dihydrofolate reductase locus from cultured mammalian cells. Urlaub, G., Käs, E., Carothers, A.M., Chasin, L.A. Cell (1983) [Pubmed]
  9. Novel submicroscopic extrachromosomal elements containing amplified genes in human cells. Maurer, B.J., Lai, E., Hamkalo, B.A., Hood, L., Attardi, G. Nature (1987) [Pubmed]
  10. Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells. Ma, C., Martin, S., Trask, B., Hamlin, J.L. Genes Dev. (1993) [Pubmed]
  11. Nuclear transport of proteins translated in vitro from SP6 plasmid-generated mRNAs. Parnaik, V.K., Kennady, P.K. Mol. Cell. Biol. (1990) [Pubmed]
  12. Heterogeneity in the specific activity and methotrexate sensitivity of dihydrofolate reductase from blast cells of acute myelogenous leukemia patients. Dedhar, S., Hartley, D., Fitz-Gibbons, D., Phillips, G., Goldie, J.H. J. Clin. Oncol. (1985) [Pubmed]
  13. Dihydrofolate reductase from Lactobacillus casei. Stereochemistry of NADPH binding. Matthews, D.A., Alden, R.A., Freer, S.T., Xuong, N., Kraut, J. J. Biol. Chem. (1979) [Pubmed]
  14. Rate and extent of interconversion of tetrahydrofolate cofactors to dihydrofolate after cessation of dihydrofolate reductase activity in stationary versus log phase L1210 leukemia cells. Trent, D.F., Seither, R.L., Goldman, I.D. J. Biol. Chem. (1991) [Pubmed]
  15. Folate-pool interconversions and inhibition of biosynthetic processes after exposure of L1210 leukemia cells to antifolates. Experimental and network thermodynamic analyses of the role of dihydrofolate polyglutamylates in antifolate action in cells. Seither, R.L., Trent, D.F., Mikulecky, D.C., Rape, T.J., Goldman, I.D. J. Biol. Chem. (1989) [Pubmed]
  16. The spatial position and replication timing of chromosomal domains are both established in early G1 phase. Dimitrova, D.S., Gilbert, D.M. Mol. Cell (1999) [Pubmed]
  17. New mechanisms of drug resistance in parasitic protozoa. Borst, P., Ouellette, M. Annu. Rev. Microbiol. (1995) [Pubmed]
  18. Structure of and kinetic channelling in bifunctional dihydrofolate reductase-thymidylate synthase. Knighton, D.R., Kan, C.C., Howland, E., Janson, C.A., Hostomska, Z., Welsh, K.M., Matthews, D.A. Nat. Struct. Biol. (1994) [Pubmed]
  19. Alpha-pyridine nucleotides as substrates for a plasmid-specified dihydrofolate reductase. Smith, S.L., Burchall, J.J. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  20. Single-molecule and transient kinetics investigation of the interaction of dihydrofolate reductase with NADPH and dihydrofolate. Zhang, Z., Rajagopalan, P.T., Selzer, T., Benkovic, S.J., Hammes, G.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  21. The matrix attachment region in the Chinese hamster dihydrofolate reductase origin of replication may be required for local chromatid separation. Mesner, L.D., Hamlin, J.L., Dijkwel, P.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  22. Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Ravanel, S., Cherest, H., Jabrin, S., Grunwald, D., Surdin-Kerjan, Y., Douce, R., Rébeillé, F. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  23. High-resolution mapping of replication fork movement through the amplified dihydrofolate reductase domain in CHO cells by in-gel renaturation analysis. Leu, T.H., Hamlin, J.L. Mol. Cell. Biol. (1989) [Pubmed]
  24. Site-specific initiation of DNA replication in Xenopus egg extract requires nuclear structure. Gilbert, D.M., Miyazawa, H., DePamphilis, M.L. Mol. Cell. Biol. (1995) [Pubmed]
  25. RIP60, a mammalian origin-binding protein, enhances DNA bending near the dihydrofolate reductase origin of replication. Caddle, M.S., Dailey, L., Heintz, N.H. Mol. Cell. Biol. (1990) [Pubmed]
  26. Methotrexate resistance in an in vivo mouse tumor due to a non-active-site dihydrofolate reductase mutation. Dicker, A.P., Waltham, M.C., Volkenandt, M., Schweitzer, B.I., Otter, G.M., Schmid, F.A., Sirotnak, F.M., Bertino, J.R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  27. Dynamics of trimethoprim bound to dihydrofolate reductase. Searle, M.S., Forster, M.J., Birdsall, B., Roberts, G.C., Feeney, J., Cheung, H.T., Kompis, I., Geddes, A.J. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  28. Crystal structure of dihydrofolate reductase from Plasmodium vivax: pyrimethamine displacement linked with mutation-induced resistance. Kongsaeree, P., Khongsuk, P., Leartsakulpanich, U., Chitnumsub, P., Tarnchompoo, B., Walkinshaw, M.D., Yuthavong, Y. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. Importance of a hydrophobic residue in binding and catalysis by dihydrofolate reductase. Mayer, R.J., Chen, J.T., Taira, K., Fierke, C.A., Benkovic, S.J. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  30. Elevation of dihydrofolate reductase, thymidylate synthetase, and thymidine kinase in cultured mammalian cells after exposure to folate antagonists. Chello, P.L., McQueen, C.A., DeAngelis, L.M., Bertino, J.R. Cancer Res. (1976) [Pubmed]
  31. Precursor binding to yeast mitochondria. A general role for the outer membrane protein Mas70p. Hines, V., Schatz, G. J. Biol. Chem. (1993) [Pubmed]
  32. Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae. Cherest, H., Thomas, D., Surdin-Kerjan, Y. J. Biol. Chem. (2000) [Pubmed]
  33. Electrostatic channeling in the bifunctional enzyme dihydrofolate reductase-thymidylate synthase. Elcock, A.H., Potter, M.J., Matthews, D.A., Knighton, D.R., McCammon, J.A. J. Mol. Biol. (1996) [Pubmed]
  34. Enhanced expression of dihydrofolate reductase by bovine kidney epithelial cells results in altered cell morphology, IGF-I responsiveness, and IGF binding protein-3 expression. Cohick, W.S., Clemmons, D.R. J. Cell. Physiol. (1994) [Pubmed]
  35. Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene. Bzik, D.J., Li, W.B., Horii, T., Inselburg, J. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  36. Rapid spontaneous dihydrofolate reductase gene amplification shown by fluorescence-activated cell sorting. Johnston, R.N., Beverley, S.M., Schimke, R.T. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  37. Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line. Nunberg, J.H., Kaufman, R.J., Schimke, R.T., Urlaub, G., Chasin, L.A. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  38. High-resolution mapping of the origin of DNA replication in the hamster dihydrofolate reductase gene domain by competitive PCR. Pelizon, C., Diviacco, S., Falaschi, A., Giacca, M. Mol. Cell. Biol. (1996) [Pubmed]
  39. Overproduction of dihydrofolate reductase and gene amplification in methotrexate-resistant Chinese hamster ovary cells. Flintoff, W.F., Weber, M.K., Nagainis, C.R., Essani, A.K., Robertson, D., Salser, W. Mol. Cell. Biol. (1982) [Pubmed]
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