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Article dans une revue

Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis.

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 I$_{320}$ 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 $\beta$6 of the Pdx1 ($\beta \alpha$)$_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 ${\AA}$ between substrate- and product-binding sites.
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Matthew J Rodrigues, Volker Windeisen, Yang Zhang, Gabriela Guédez, Stefan Weber, et al.. Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis.. Nature Chemical Biology, Nature Publishing Group, 2017, 13 (3), pp.290-294. ⟨10.1038/nchembio.2273⟩. ⟨hal-01487798⟩

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