S-Adenosyl-l-ethionine is a Catalytically Competent Analog of S-Adenosyl-l-methionine (SAM) in the Radical SAM Enzyme HydG

Stella Impano, Hao Yang, Eric M. Shepard, Ryan Swimley, Adrien Pagnier, William E. Broderick, Brian M. Hoffman, Joan B. Broderick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Radical S-adenosyl-l-methionine (SAM) enzymes initiate biological radical reactions with the 5′-deoxyadenosyl radical (5′-dAdo.). A [4Fe-4S]+ cluster reductively cleaves SAM to form the Ω organometallic intermediate in which the 5′-deoxyadenosyl moiety is directly bound to the unique iron of the [4Fe-4S] cluster, with subsequent liberation of 5′-dAdo.. We present synthesis of the SAM analog S-adenosyl-l-ethionine (SAE) and show SAE is a mechanistically equivalent SAM-alternative for HydG, both supporting enzymatic turnover of substrate tyrosine and forming the organometallic intermediate Ω. Photolysis of SAE-bound HydG forms an ethyl radical trapped in the active site. The ethyl radical withstands prolonged storage at 77 K and its EPR signal is only partially lost upon annealing at 100 K, making it significantly less reactive than the methyl radical formed by SAM photolysis. Upon annealing above 77 K, the ethyl radical adds to the [4Fe-4S]2+ cluster, generating an ethyl-[4Fe-4S]3+ organometallic species termed ΩE.

Original languageEnglish (US)
Pages (from-to)4666-4672
Number of pages7
JournalAngewandte Chemie - International Edition
Issue number9
StatePublished - Feb 23 2021


  • EPR spectroscopy
  • S-adenosylethionine
  • ethyl radicals
  • organometallic chemistry
  • radical SAM

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)


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