A 1H n.m.r. study of the role of the glutamate moiety in the binding of methotrexate to Lactobacillus casei dihydrofolate reductase

Br J Pharmacol. 1984 Feb;81(2):309-15. doi: 10.1111/j.1476-5381.1984.tb10080.x.


The binding of a series of amide derivatives of methotrexate to Lactobacillus casei dihydrofolate reductase has been studied by inhibition constant measurements and by 1H n.m.r. spectroscopy. Amide modification of the alpha-carboxylate of methotrexate was found to prevent interaction of the gamma-carboxylate with the imidazole of His 28. Estimates of the contributions to the binding energy from the alpha-carboxylate-Arg 57 and gamma-carboxylate-His 28 interactions have been made from a combination of inhibition and n.m.r. data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Folic Acid Antagonists
  • Glutamates / metabolism*
  • Histidine / metabolism
  • Lactobacillus casei / enzymology*
  • Magnetic Resonance Spectroscopy
  • Methotrexate / analogs & derivatives
  • Methotrexate / metabolism*
  • Methotrexate / pharmacology
  • Protein Binding
  • Tetrahydrofolate Dehydrogenase / metabolism*


  • Folic Acid Antagonists
  • Glutamates
  • Histidine
  • methotrexate-gamma-monoamide
  • methotrexate-alpha-monoamide
  • Tetrahydrofolate Dehydrogenase
  • Methotrexate