Characterization of a new feedback-resistant 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase AroF of Escherichia coli

FEMS Microbiol Lett. 2001 Aug 7;202(1):145-8. doi: 10.1111/j.1574-6968.2001.tb10795.x.

Abstract

Tyrosine feedback-inhibits the 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase isoenzyme AroF of Escherichia coli. Here we show that an Asn-8 to Lys-8 substitution in AroF leads to a tyrosine-insensitive DAHP synthase. This mutant enzyme exhibited similar activities (v=30-40 U mg(-1)) and substrate affinities (K(m)(erythrose-4-phosphate)=0.5 mM, positive cooperativity with respect to phospho(enol)pyruvate) as the wild-type AroF, but showed decreased thermostability. An engineered AroF enzyme lacking the seven N-terminal residues also was tyrosine-resistant. These results strongly suggest that the N-terminus of AroF is involved in the molecular interactions occurring in the feedback-inhibition mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Deoxy-7-Phosphoheptulonate Synthase / chemistry
  • 3-Deoxy-7-Phosphoheptulonate Synthase / genetics
  • 3-Deoxy-7-Phosphoheptulonate Synthase / metabolism*
  • Alleles
  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Enzyme Stability
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Feedback, Physiological / drug effects
  • Kinetics
  • Mutation / genetics
  • Sequence Homology, Amino Acid
  • Sugar Phosphates / metabolism*
  • Temperature
  • Tyrosine / metabolism
  • Tyrosine / pharmacology

Substances

  • Sugar Phosphates
  • 3-deoxy-D-arabino-heptulosonate-7-phosphate
  • Tyrosine
  • 3-Deoxy-7-Phosphoheptulonate Synthase