Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis

• Verfasst von: Rodrigues, Matthew [VerfasserIn]
• Verfasst von: Windeisen, Volker [VerfasserIn]
• Verfasst von: Guédez Rodríguez, Gabriela Liuvanova [VerfasserIn]
• Verfasst von: Strohmeier, Marco [VerfasserIn]
• Verfasst von: Sinning, Irmgard [VerfasserIn]
• Verfasst von: Tews, Ivo [VerfasserIn]
• Titel: Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis
• Verf.angabe: 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
• E-Jahr: 2017
• Jahr: 23 January 2017
• Umfang: 5 S.
• Fussnoten: Gesehen am 19.07.2018
• Titel Quelle: Enthalten in: Nature chemical biology
• Ort Quelle: Basingstoke : Nature Publishing Group, 2005
• Jahr Quelle: 2017
• Band/Heft Quelle: 13(2017), 3, Seite 290-294
• ISSN Quelle: 1552-4469
• DOI: doi:10.1038/nchembio.2273
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 157777065X

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 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.