A 1H n.m.r. study of the role of the glutamate moiety in the binding of methotrexate to Lactobacillus casei dihydrofolate reductase
Open Access
- 1 February 1984
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 81 (2) , 309-315
- https://doi.org/10.1111/j.1476-5381.1984.tb10080.x
Abstract
1 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. 2 Amide modification of the α-carboxylate of methotrexate was found to prevent interaction of the γ-carboxylate with the imidazole of His 28. 3 Estimates of the contributions to the binding energy from the α-carboxylate-Arg 57 and γ-carboxylate-His 28 interactions have been made from a combination of inhibition and n.m.r. data.This publication has 22 references indexed in Scilit:
- Receptor-based design of dihydrofolate reductase inhibitors: comparison of crystallographically determined enzyme binding with enzyme affinity in a series of carboxy-substituted trimethoprim analogsJournal of Medicinal Chemistry, 1982
- Methotrexate analogs. 14. Synthesis of new .gamma.-substituted derivatives as dihydrofolate reductase inhibitors and potential anticancer agentsJournal of Medicinal Chemistry, 1981
- Effect of coenzyme binding on histidine residues of Lactobacillus casei dihydrofolate reductaseBiochemistry, 1981
- Histidine residues of Lactobacillus casei dihydrofolate reductase: paramagnetic relaxation and deuterium-exchange studies and partial assignmentsBiochemistry, 1980
- Dihydrofolate Reductase: X-ray Structure of the Binary Complex with MethotrexateScience, 1977
- 1 H nuclear magnetic resonance studies of Lactobacillus casei dihydrofolate reductase: effects of substrate and inhibitor binding on the histidine residuesProceedings of the Royal Society of London. B. Biological Sciences, 1977
- Nuclear magnetic resonance studies of the binding of substrate analogs and coenzyme to dihydrofolate reductase from Lactobacillus caseiBiochemistry, 1974
- Methotrexate analogs. 3. Synthesis and biological properties of some side-chain altered analogsJournal of Medicinal Chemistry, 1974
- Analogs of Pteroylglutamic Acid. III. 4-Amino DerivativesJournal of the American Chemical Society, 1949
- Isolation and Characterization of Vitamin Bc from Liver and Yeast.1 Occurrence of an Acid-labile Chick Antianemia Factor in LiverJournal of the American Chemical Society, 1947