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

9 Citations (Scopus)

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 (SAM CA ), in which the ACP group of SAM is replaced with a 3-carboxyallyl group. SAM CA 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 13 C and 2 H isotopically labeled SAM CA 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

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S-Adenosylmethionine
Organometallics
Enzymes
Acids
Biosynthesis
Pyrococcus horikoshii
Reaction products
Olefins
Iron
Electrons
Electron Spin Resonance Spectroscopy
Alkenes

All Science Journal Classification (ASJC) codes

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

Cite this

Dong, Min ; Horitani, Masaki ; Dzikovski, Boris ; Pandelia, Maria Eirini ; Krebs, Carsten ; Freed, Jack H. ; Hoffman, Brian M. ; Lin, Hening. / Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme. In: Journal of the American Chemical Society. 2016 ; Vol. 138, No. 31. pp. 9755-9758.
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Dong, M, Horitani, M, Dzikovski, B, Pandelia, ME, Krebs, C, Freed, JH, Hoffman, BM & Lin, H 2016, 'Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme', Journal of the American Chemical Society, vol. 138, no. 31, pp. 9755-9758. https://doi.org/10.1021/jacs.6b04155

Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme. / Dong, Min; Horitani, Masaki; Dzikovski, Boris; Pandelia, Maria Eirini; Krebs, Carsten; Freed, Jack H.; Hoffman, Brian M.; Lin, Hening.

In: Journal of the American Chemical Society, Vol. 138, No. 31, 10.08.2016, p. 9755-9758.

Research output: Contribution to journalArticle

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