Substrate and inhibitor binding to dihydrofolate reductase

  • G. C. K. Roberts
Part of the Biological Council book series (BCSDA)


Dihydrofolate reductase (5, 6, 7, 8-tetrahydrofolate:NADP+ oxidoreductase, E.C., an enzyme found in the vast majority of both prokaryotic and eukaryotic organisms, catalyses the reduction of dihydrofolate to tetrahydrofolate, using NADPH as coenzyme:
The product of this reaction, tetrahydrofolate, plays a vital role in intermediary metabolism, acting as a ‘carrier’ of one-carbon fragments in the biosynthesis of a number of amino acids, thymidylate and purines (for a review, see Blakley, 1969).


Tyrosine Residue Folinic Acid Histidine Residue Nuclear Magnetic Reson Spectroscopy Dihydrofolate Reductase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Baker, B. R. (1959). Cancer Chemother. Rep., 4, 1Google Scholar
  2. Baker, B. R. (1967). Design of Active -site -directed Irreversible Enzyme Inhibitors, New York, WileyGoogle Scholar
  3. Baker, B. R., Santi, D. V., Almaula, P. I. and Werkheiser, W. C. (1964). J. Med. Chem., 7, 24PubMedCrossRefGoogle Scholar
  4. Baker, B. R., Schwan, T. J., Novotny, J. and Ho, B. T. (1966). J. Pharm. Sci., 55, 295PubMedCrossRefGoogle Scholar
  5. Baugh, C. M., Braverman, E. and Nair, M. G. (1974). Biochemistry, 13, 4952PubMedCrossRefGoogle Scholar
  6. Bertino, J. R. (Ed.) (1971). Folate antagonists as chemotherapeutic agents. Ann. N. Y. Acad. Sci., 186Google Scholar
  7. Birdsall, B., Feeney, J., Roberts, G. C. K. and Burgen, A. S. V. (1977a). Manuscript in preparationGoogle Scholar
  8. Birdsall, B., Griffiths, D. V., Roberts, G. C. K., Feeney, J. and Burgen, A. S. V. (1977b). Proc. R. Soc. London, in press.Google Scholar
  9. Blakley, R. L. (1969). The Biochemistry of Folic Acid and Related Pteridines. Amsterdam, North -HollandGoogle Scholar
  10. Brown, J. P., Dobbs, F., Davidson, G.E. and Scott, J. M. (1974). J. Gen. Microbiol., 84, 163PubMedCrossRefGoogle Scholar
  11. Buehring, K. U., Tamura, T. and Stokstad, E. L. R. (1974). J. Biol. Chem., 249, 1081PubMedGoogle Scholar
  12. Burchall, J. J. (1971). Ann. N. Y. Acad. Sci., 186, 143PubMedCrossRefGoogle Scholar
  13. Burchall, J. J. and Hitchings, G. H. (1965). Mol. Pharmacol., 1, 126PubMedGoogle Scholar
  14. Chaykovsky, M., Rosowsky, A., Papathanasopoulos, N., Chen, K. K. N., Modest, E. J., Kisliuk, R. L. and Gaumont, Y. (1974) J. Med. Chem., 17, 1212PubMedCrossRefGoogle Scholar
  15. Collin, R., and Pullman, B. (1964). Biochim. Biophys. Acta, 89, 232PubMedGoogle Scholar
  16. Dann, J. G., Ostler, G., Bjur, R. A., King, R. W., Scudder, P., Turner, P. C., Roberts, G. C. K., Burgen, A. S. V. and Harding, N. G. L. (1976). Biochem. J., 157, 559PubMedPubMedCentralCrossRefGoogle Scholar
  17. Erickson, J. S. and Mathews, C. K. (1972). J. Biol. Chem., 247, 5661PubMedGoogle Scholar
  18. Farber, S., Diamond, L. K., Mercer, R. D., Sylvester, R. J. Jr. and Wolff, J. A. (1948). New Engl. J. Med., 238, 787PubMedCrossRefGoogle Scholar
  19. Feeney, J., Birdsall, B., Roberts, G. C. K. and Burgen, A. S. V. (1975). Nature (London), 257, 564CrossRefGoogle Scholar
  20. Feeney, J., Roberts, G. C. K., Birdsall, B., Griffiths, D. V., King, R. W., Scudder, P. and Burgen, A. S. V. (1977). Proc. R. Soc. London, in pressGoogle Scholar
  21. Ferone, R., Burchall, J. J. and Hitchings, G. H. (1969). Mol. Pharmacol., 5, 49PubMedGoogle Scholar
  22. Ferone, R., O’Shea, M. and Yoeli, M. (1970). Science, N. Y., 167, 1263CrossRefGoogle Scholar
  23. Futterman, S. (1957). J. Biol. Chem., 228, 1031PubMedGoogle Scholar
  24. Goldman, I. D. (1971). Ann. N. Y. Acad. Sci., 186, 400PubMedCrossRefGoogle Scholar
  25. Greenberg, D. M., Tam, B. D., Jenny, E. and Payes, B. (1966). Biochim. Biophys. Acta, 122, 423CrossRefGoogle Scholar
  26. Greenfield, N. J. (1975). Biochim. Biophys. Acta, 403, 32PubMedCrossRefGoogle Scholar
  27. Hakala, M. T., Zakrzewski, S.F. and Nichol, C. A. (1961). J. Biol. Chem., 236, 952PubMedGoogle Scholar
  28. Harrap, K. R., Hill, B. T., Furness, M. E. and Hart, L. I. (1971). Ann. N. Y. Acad. Sci., 186, 312PubMedCrossRefGoogle Scholar
  29. Hitchings, G. H. and Burchall, J. J. (1965). Adv. Enzymol., 27, 417PubMedGoogle Scholar
  30. Hitchings, G. H., Falco, E. A., Vanderwerff, H., Russell, P. B. and Elion, G. B. (1952). J. Biol. Chem., 199, 43PubMedGoogle Scholar
  31. Hutchison, D. J. (1971). Ann. N. Y. Acad. Sci., 186, 172PubMedCrossRefGoogle Scholar
  32. Jencks, W. P. (1975). Adv. Enzymol., 43, 219PubMedGoogle Scholar
  33. Johns, D. G., Ianotti, A. T., Sartorelli, A. C. and Bertino, J. R. (1966). Biochem. Pharm., 15, 555PubMedCrossRefGoogle Scholar
  34. Johns, D. G., and Valerino, D. M. (1971). Ann. N. Y. Acad. Sci., 186, 378PubMedCrossRefGoogle Scholar
  35. Mihich, E. (Ed.) (1973). Drug Resistance and Sensitivity: Biochemical and Cellular Basis, New York, Academic PressGoogle Scholar
  36. Nichol, C. A. and Welch, A. D. (1950). Proc. Soc. Exp. Biol. Med., 74, 403PubMedCrossRefGoogle Scholar
  37. Osborn, M. J., Freeman, M. and Huennekens, F. M. (1958). Proc. Soc. Exp. Biol. Med., 97, 429PubMedCrossRefGoogle Scholar
  38. Perault, A. M. and Pullman, B. (1961). Biochim. Biophys. Acta, 52, 266PubMedCrossRefGoogle Scholar
  39. Perkins, J. R. and Bertino, J. R. (1966). Biochemistry, 5, 1005PubMedCrossRefGoogle Scholar
  40. Plante, L. T., Crawford, E. J. and Friedkin, M. (1967). J. Biol. Chem., 242, 1466PubMedGoogle Scholar
  41. Poe, M., Bennett, C. D., Donoghue, D., Hirshfield, J. M., Williams, M. N. and Hoogsteen, K. (1975). In Chemistry and Biology of Pteridines (Proc. 5th Int. Symp.) (ed. W. Pfleiderer ), p. 51Google Scholar
  42. Poe, M., Greenfield, N. J., Hirshfield, J. M. and Hoogsteen, K. (1974). Cancer Biochem. Biophys., 1, 7Google Scholar
  43. Roberts, G. C. K., Feeney, J., Burgen, A. S. V., Yuferov, V., Dann, J. G. and Bjur, R. A. (1974). Biochemistry, 13, 5351PubMedCrossRefGoogle Scholar
  44. Seeger, D. R., Smith, J. M. Jr. and Hultquist, M. E. (1947). J. Am. Chem. Soc., 69, 2567PubMedCrossRefGoogle Scholar
  45. Way, J. L., Birdsall, B., Feeney, J., Roberts, G. C. K. and Burgen, A. S. V. (1975). Biochemistry, 14, 3470PubMedCrossRefGoogle Scholar
  46. Weber, G. (1975). Adv. Protein Chem., 29, 1PubMedCrossRefGoogle Scholar
  47. Zakrzewski, S.F. (1963). J. Biol. Chem., 238, 1485PubMedGoogle Scholar
  48. Zakrzewski, S. F. and Nichol, C. A. (1958). Biochim. Biophys. Acta, 27, 425PubMedCrossRefGoogle Scholar

Copyright information

© Institute of Biology Endowment Trust Fund 1977

Authors and Affiliations

  • G. C. K. Roberts
    • 1
  1. 1.Division of Molecular PharmacologyNational Institute for Medical ResearchLondonUK

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