6bxo

Publication Abstract from PubMed

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.

Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis.,Dong M, Kathiresan V, Fenwick MK, Torelli AT, Zhang Y, Caranto JD, Dzikovski B, Sharma A, Lancaster KM, Freed JH, Ealick SE, Hoffman BM, Lin H Science. 2018 Mar 16;359(6381):1247-1250. doi: 10.1126/science.aao6595. PMID:29590073^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.