Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis Academic Article uri icon

abstract

  • 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 6 of the Pdx1 ()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 between substrate- and product-binding sites.

published proceedings

  • Nat Chem Biol

altmetric score

  • 18.05

author list (cited authors)

  • Rodrigues, M. J., Windeisen, V., Zhang, Y., Gudez, G., Weber, S., Strohmeier, M., ... Tews, I.

citation count

  • 15

complete list of authors

  • Rodrigues, Matthew J||Windeisen, Volker||Zhang, Yang||Gu├ędez, Gabriela||Weber, Stefan||Strohmeier, Marco||Hanes, Jeremiah W||Royant, Antoine||Evans, Gwyndaf||Sinning, Irmgard||Ealick, Steven E||Begley, Tadhg P||Tews, Ivo

publication date

  • January 1, 2017 11:11 AM