Dihydrofolate Reductase

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Lactobacillus casei dihydrofolate reductase

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 'H n.m.r. spectroscopy. 2 Amide modification of the a-carboxylate of methotrexate was found to prevent interaction of the y-carboxylate with the imidazole of His 28. 3 Estimates of the contributions to the binding energy from t...

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Dihydrofolate reductase from Neisseria sp.

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...

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Life without dihydrofolate reductase FolA.

Reduced folate derivatives participate in numerous reactions of bacterial intermediary metabolism. Consequently, the well-characterized enzyme implicated in the formation of tetrahydrofolate--dihydrofolate reductase FolA--was considered to be essential for bacterial growth. However, comparative genomics has revealed several bacterial genome sequences that appear to lack the folA gene. Here, we ...

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Tales of Dihydrofolate Binding to R67 Dihydrofolate Reductase

Homotetrameric R67 dihydrofolate reductase possesses 222 symmetry and a single active site pore. This situation results in a promiscuous binding site that accommodates either the substrate, dihydrofolate (DHF), or the cofactor, NADPH. NADPH interacts more directly with the protein as it is larger than the substrate. In contrast, the p-aminobenzoyl-glutamate tail of DHF, as monitored by nuclear ...

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Effects of 5-fluorouracil on dihydrofolate reductase and dihydrofolate reductase mRNA from methotrexate-resistant KB cells.

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...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 1973

ISSN: 0021-9258

DOI: 10.1016/s0021-9258(19)44361-5