Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis.

نویسندگان

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

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.

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عنوان ژورنال:
  • Nature chemical biology

دوره 13 3  شماره 

صفحات  -

تاریخ انتشار 2017