Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme

Min Dong, Masaki Horitani, Boris Dzikovski, Maria Eirini Pandelia, Carsten Krebs, Jack H. Freed, Brian M. Hoffman, Hening Lin

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Pyrococcus horikoshii Dph2 (PhDph2) is an unusual radical S-adenosylmethionine (SAM) enzyme involved in the first step of diphthamide biosynthesis. It catalyzes the reaction by cleaving SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. To probe the reaction mechanism, we synthesized a SAM analogue (SAMCA), in which the ACP group of SAM is replaced with a 3-carboxyallyl group. SAMCA is cleaved by PhDph2, yielding a paramagnetic (S = 1/2) species, which is assigned to a complex formed between the reaction product, α-sulfinyl-3-butenoic acid, and the [4Fe-4S] cluster. Electron-nuclear double resonance (ENDOR) measurements with 13C and 2H isotopically labeled SAMCA support a π-complex between the C=C double bond of α-sulfinyl-3-butenoic acid and the unique iron of the [4Fe-4S] cluster. This is the first example of a radical SAM-related [4Fe-4S]+ cluster forming an organometallic complex with an alkene, shedding additional light on the mechanism of PhDph2 and expanding our current notions for the reactivity of [4Fe-4S] clusters in radical SAM enzymes.

Original languageEnglish (US)
Pages (from-to)9755-9758
Number of pages4
JournalJournal of the American Chemical Society
Volume138
Issue number31
DOIs
StatePublished - Aug 10 2016

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Dong, M., Horitani, M., Dzikovski, B., Pandelia, M. E., Krebs, C., Freed, J. H., Hoffman, B. M., & Lin, H. (2016). Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme. Journal of the American Chemical Society, 138(31), 9755-9758. https://doi.org/10.1021/jacs.6b04155