Growth of methotrexate-resistant dihydrofolate reductase gene-amplified KB cells in the presence of 5-fluorouracil results in an increase in dihydrofolate reductase mRNA. This increase can be solely attributed to a species of RNA of approximately 3.5 kilobase pairs in size. Although dihydrofolate reductase enzyme activity increases per cell with increasing 5-fluorouracil, there is a decrease of...

Members of the genus Neisseria are relatively nonsusceptible to trimethoprim, an inhibitor of dihydrofolate reductase. For example, the minimal inhibitory concentration (MIC) of trimethoprim for N. gonorrhoeae ranges from 2 to 70 mug/ml, whereas the MIC for Escherichia coli is 0.2 mug/ml or less. In an effort to understand this difference, dihydrofolate reductase was partially purified from fiv...

Plasmodium falciparum dihydrofolate reductase is an important target for antimalarial chemotherapy. The emergence of resistance has significantly reduced the efficacy of the classic antifolate drugs cycloguanil and pyrimethamine. In this paper we report new dihydrofolate reductase inhibitors identified using molecular modelling principles with the goal of designing new antifolate agents active ...

Mutants of Chinese hamster ovary cells lacking dihydrofolate reductase (tetrahydrofolate dehydrogenase, 7,8-dihydrofolate:NADP+ oxidoreductase; EC 1.5.1.3) activity were isolated after mutagenesis and exposure to high-specific-activity [3H]deoxyuridine as a selective agent. Fully deficient mutants could not be isolated starting with wild-type cells, but could readily be selected from a putative...

A plasmid-encoded dihydrofolate reductase that originated in a clinical isolate of Salmonella typhimurium (phage type 179) moderately resistant to trimethoprim has been isolated and characterized. The dihydrofolate reductase (called type III) was purified to homogeneity using a combination of gel filtration, hydrophobic chromatography, and methotrexate affinity chromatography. Polyacrylamide ge...

It is shown by analysis of a cyclic enzymatic network that the presence zero net flux/current cycles impose strong thermodynamic constraints on values kinetic parameters. Thermodynamic carried out for four-node pyramidal reaction involving conversion 7,8-­dihydrofolate (H2F) and NADPH in H+ to 5,6,7,8-­tetrahydrofolate (H4F) NADP+ catalyzed universal enzyme dihydrofolate reductase (DHFR). The c...

Dihydrofolate reductase has been isolated and purified to homogeneity in g6od yield from two trimethoprim-resistant strains of Escherichia coli K12, strains MB 3746 and MB 3747. The two enzymes are closely related to one another and to the dihydrofolate reductase from E. coli MB 1428. The 3746 and 3747 reductases both exhibit an apparent molecular weight of 17,500 with almost identical amino ac...