Regulatory mutants of dihydrofolate reductase in Escherichia coli K12.
Trimethoprim inhibits dihydrofolate reductase. Mutations conferring trimethorpim-resistance on E coli K12 result in either an altered reductase with decreased affinity for the drug, or in 2-30 fold higher levels of the enzyme. Studies of the latter class of mutants indicate that dihydrofolate reductase is regulatdd by a diffusible molecule, and is probably under negative control. The regulatrory mutants, some of which are temperature-sensitive, act cis.
D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D005493:Folic Acid Antagonists; D005838:Genotype; D008727:Methotrexate / Q000494:pharmacology; D009154:Mutation; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D014295:Trimethoprim / Q000494:pharmacology*
D005493:Folic Acid Antagonists; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate