Spectroscopic approaches to elucidating novel iron-sulfur chemistry in the "radical-SAM" protein superfamily

Charles J. Walsby, Danilo Ortillo, Jian Yang, Mbako R. Nnyepi, William E. Broderick, Brian M. Hoffman, Joan B. Broderick*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

93 Scopus citations


Electron paramagnetic resonance (EPR), electron-nuclear double resonance (ENDOR), and Mössbauer spectroscopies and other physical methods have provided important new insights into the radical-SAM superfamily of proteins, which use iron-sulfur clusters and S-adenosylmethionine to initiate H atom abstraction reactions. This remarkable chemistry involves the generation of the extremely reactive 5′-deoxyadenosyl radical, the same radical intermediate utilized in B12-dependent reactions. Although early speculation focused on the possibility of an organometallic intermediate in radical-SAM reactions, current evidence points to novel chemistry involving a site-differentiated [4Fe-4S] cluster. The focus of this forum article is on one member of the radical-SAM superfamily, pyruvate formate-lyase activating enzyme, and how physical methods, primarily EPR and ENDOR spectroscopies, are contributing to our understanding of its structure and mechanism. New ENDOR data supporting coordination of the methionine moiety of SAM to the unique site of the [4Fe-4S]2+/+ cluster are presented.

Original languageEnglish (US)
Pages (from-to)727-741
Number of pages15
JournalInorganic chemistry
Issue number4
StatePublished - Feb 21 2005

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry


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