Jan 15, 1976

The purification and properties of the trimethoprim-resistant dihydrofolate reductase mediated by the R-factor, R388

European Journal of Biochemistry
S G Amyes, J T Smith

Abstract

The R-factor R388 mediates the production of a trimethoprim-resistant dihydrofolate reductase. This enzyme has a different molecular weight and pH profile to the trimethoprim-sensitive enzyme of the Escherichia coli host. The R-factor mediated enzyme was separated completely from the host E. coli enzyme by DEAE-cellulose ion-exchange chromatography. The purified R-factor enzyme was about 20 000 times less susceptible to trimethoprim than the E. coli enzyme and although it was inhibited competitively by trimethoprim, its inhibitor constant (Ki) was 20 000 times greater than that of the host enzyme. The R388 and E. coli enzymes also differed in their substrate specificity requirements. In addition, the R388 enzyme suprisingly conferred high level resistance to the broad spectrum dihydrofolate reductase inhibitor, amethopterin. The possible origins of the R388 enzyme are discussed.

  • References8
  • Citations24

References

  • References8
  • Citations24

Mentioned in this Paper

Antibiotic Resistance, Microbial
Alkalescens-Dispar Group
DHFR
Tetrahydrofolate Dehydrogenase
Methotrexate, (DL)-Isomer
Hydrogen-Ion Concentration
Trimpex
Folic Acid Antagonists

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