Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis
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 chemi...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
23 January 2017
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| In: |
Nature chemical biology
Year: 2017, Volume: 13, Issue: 3, Pages: 290-294 |
| ISSN: | 1552-4469 |
| DOI: | 10.1038/nchembio.2273 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/nchembio.2273 Verlag, Volltext: https://www.nature.com/articles/nchembio.2273 
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| Author Notes: | 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 |
| Summary: | 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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| Item Description: | Gesehen am 19.07.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1552-4469 |
| DOI: | 10.1038/nchembio.2273 |