Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human gammadelta T cells in Escherichia coli

FEBS Lett. 2001 Dec 7;509(2):317-22. doi: 10.1016/s0014-5793(01)03191-x.

Abstract

The gcpE and lytB gene products control the terminal steps of isoprenoid biosynthesis via the 2-C-methyl-D-erythritol 4-phosphate pathway in Escherichia coli. In lytB-deficient mutants, a highly immunogenic compound accumulates significantly, compared to wild-type E. coli, but is apparently absent in gcpE-deficient mutants. Here, this compound was purified from E. coli DeltalytB mutants by preparative anion exchange chromatography, and identified by mass spectrometry, (1)H, (13)C and (31)P NMR spectroscopy, and NOESY analysis as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP). HMB-PP is 10(4) times more potent in activating human Vgamma9/Vdelta2 T cells than isopentenyl pyrophosphate.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Diphosphates / chemistry
  • Diphosphates / pharmacology*
  • Enzymes*
  • Erythritol / analogs & derivatives*
  • Erythritol / biosynthesis
  • Escherichia coli / chemistry*
  • Escherichia coli Proteins*
  • Humans
  • Lymphocyte Activation / drug effects*
  • Mitogens / chemistry
  • Mitogens / pharmacology*
  • Models, Biological
  • Nuclear Magnetic Resonance, Biomolecular
  • Oxidoreductases*
  • Receptors, Antigen, T-Cell, gamma-delta*
  • Spectrometry, Mass, Electrospray Ionization
  • Sugar Phosphates / biosynthesis
  • T-Lymphocyte Subsets / drug effects*
  • Terpenes / metabolism

Substances

  • 2-C-methylerythritol 4-phosphate
  • 4-hydroxy-3-methylbut-2-enyl pyrophosphate
  • Bacterial Proteins
  • Diphosphates
  • Enzymes
  • Escherichia coli Proteins
  • Mitogens
  • Receptors, Antigen, T-Cell, gamma-delta
  • Sugar Phosphates
  • Terpenes
  • hydroxymethylbutenyl 4-diphosphate synthase
  • Oxidoreductases
  • ispH protein, E coli
  • Erythritol