Salicylate biosynthesis in Pseudomonas aeruginosa. Purification and characterization of PchB, a novel bifunctional enzyme displaying isochorismate pyruvate-lyase and chorismate mutase activities

J Biol Chem. 2002 Jun 14;277(24):21768-75. doi: 10.1074/jbc.M202410200. Epub 2002 Apr 5.

Abstract

Isochorismate pyruvate-lyase (IPL), the second enzyme of pyochelin biosynthesis and the product of the pchB gene, was purified to homogeneity from Pseudomonas aeruginosa. In the reaction catalyzed by this enzyme, isochorismate --> salicylate + pyruvate, no cofactors appear to be required. At the pH optimum (pH 6.8), the enzyme displayed Michaelis-Menten kinetics, with an apparent K(m) of 12.5 microm for isochorismate and a kcat of 106 min(-1), calculated per monomer. The native enzyme behaved as a homodimer, as judged by molecular sieving chromatography, electrophoresis under nondenaturing conditions, and cross-linking experiments. PchB has approximately 20% amino acid sequence identity with AroQ-class chorismate mutases (CMs). Chorismate was shown to be converted to prephenate by purified PchB in vitro, with an apparent K(m) of 150 microm and a kcat of 7.8 min(-1). An oxabicyclic diacid transition state analog and well characterized inhibitor of CMs competitively inhibited both IPL and CM activities of PchB. Moreover, a CM-deficient Escherichia coli mutant, which is auxotrophic for phenylalanine and tyrosine, was functionally complemented by the cloned P. aeruginosa pchB gene for growth in minimal medium. A mutant form of PchB, in which isoleucine 88 was changed to threonine, had no detectable IPL activity, but retained wild-type CM activity. In conclusion, the 11.5-kDa subunit of PchB appears to contain a single active site involved in both IPL and CM activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / isolation & purification*
  • Binding, Competitive
  • Blotting, Western
  • Catalysis
  • Chromatography, High Pressure Liquid
  • Cross-Linking Reagents / pharmacology
  • Dimerization
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / metabolism
  • Genetic Complementation Test
  • Hydrogen-Ion Concentration
  • Isoleucine / chemistry
  • Kinetics
  • Models, Chemical
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Pseudomonas aeruginosa / enzymology*
  • Salicylates / metabolism*
  • Temperature

Substances

  • Bacterial Proteins
  • Cross-Linking Reagents
  • Salicylates
  • pchB protein, Pseudomonas aeruginosa
  • Isoleucine