Characterization and inhibition of dihydrofolate synthetase from Neisseria gonorrhoeae

Mol Cell Biochem. 1984;59(1-2):165-71. doi: 10.1007/BF00231312.

Abstract

Dihydrofolate synthetase (EC 6.3.2.12) from N. gonorrhoeae was isolated and enzyme characteristics were determined. The purified enzyme was found quite stable when stored at -60 degrees C. About 50% of the enzyme activity was destroyed within 6 weeks when kept at 4 degrees C. Maximum velocity was observed at pH 9.3. The enzyme required a monovalent cation, K+ or NH4+, and divalent cation, Mg2+ or Mn2+, for its function. ATP at 5 mM concentration gave maximum activity. Km values for dihydropteroate and L-glutamate at pH 9.3 were 3.5 X 10(-5) M and 6.5 X 10(-4) M, respectively. Patterns of product inhibition by dihydrofolate were found to be non-competitive with respect to dihydropteroate, having a Ki value of 5.1 +/- 0.8 X 10(-4) M, and competitive with respect to L-glutamate, having a Ki value of 6.2 X 10(-4) M.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenine Nucleotides / pharmacology
  • Cations, Divalent / pharmacology
  • Cations, Monovalent / pharmacology
  • Kinetics
  • Neisseria gonorrhoeae / drug effects
  • Neisseria gonorrhoeae / enzymology*
  • Peptide Synthases / analysis*
  • Peptide Synthases / antagonists & inhibitors
  • Peptide Synthases / isolation & purification

Substances

  • Adenine Nucleotides
  • Cations, Divalent
  • Cations, Monovalent
  • Peptide Synthases
  • dihydrofolate synthetase