Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis

Nat Chem Biol. 2017 Mar;13(3):290-294. doi: 10.1038/nchembio.2273. Epub 2017 Jan 16.


Substrate channeling has emerged as a common mechanism for enzymatic intermediate transfer. A conspicuous gap in knowledge concerns the use of covalent lysine imines in the transfer of carbonyl-group-containing intermediates, despite their wideuse in enzymatic catalysis. Here we show how imine chemistry operates in the transfer of covalent intermediates in pyridoxal 5'-phosphate biosynthesis by the Arabidopsis thaliana enzyme Pdx1. An initial ribose 5-phosphate lysine imine is converted to the chromophoric I320 intermediate, simultaneously bound to two lysine residues and partially vacating the active site, which creates space for glyceraldehyde 3-phosphate to bind. Crystal structures show how substrate binding, catalysis and shuttling are coupled to conformational changes around strand β6 of the Pdx1 (βα)8-barrel. The dual-specificity active site and imine relay mechanism for migration of carbonyl intermediates provide elegant solutions to the challenge of coordinating a complex sequence of reactions that follow a path of over 20 Å between substrate- and product-binding sites.

MeSH terms

  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / metabolism
  • Carbon-Nitrogen Lyases
  • Lysine / chemistry
  • Lysine / metabolism*
  • Models, Molecular
  • Molecular Structure
  • Nitrogenous Group Transferases / chemistry
  • Nitrogenous Group Transferases / metabolism
  • Vitamin B 6 / biosynthesis*
  • Vitamin B 6 / chemistry


  • Arabidopsis Proteins
  • Vitamin B 6
  • Nitrogenous Group Transferases
  • Carbon-Nitrogen Lyases
  • At2g38230 protein, Arabidopsis
  • Lysine