| Literature DB >> 29590073 |
Min Dong1, Venkatesan Kathiresan2, Michael K Fenwick1, Andrew T Torelli1, Yang Zhang1, Jonathan D Caranto1, Boris Dzikovski1, Ajay Sharma2, Kyle M Lancaster1, Jack H Freed1, Steven E Ealick3, Brian M Hoffman4, Hening Lin3,5.
Abstract
Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe-C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C-S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C-S bond cleavage is achieved in this radical SAM enzyme.Entities:
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Year: 2018 PMID： 29590073 PMCID： PMC6066404 DOI： 10.1126/science.aao6595
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728