Metalloproteins: Radical SAM catalysis via an organometallic intermediate with an Fe-[5′-C]-deoxyadenosyl bond

Masaki Horitani, Krista Shisler, William E. Broderick, Rachel U. Hutcheson, Kaitlin S. Duschene, Amy R. Marts, Brian M. Hoffman*, Joan B. Broderick

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to cleave SAM to initiate diverse radical reactions. These reactions are thought to involve the 5′-deoxyadenosyl radical intermediate, which has not yet been detected. We used rapid freeze-quenching to trap a catalytically competent intermediate in the reaction catalyzed by the radical SAM enzyme pyruvate formate-lyase activating enzyme. Characterization of the intermediate by electron paramagnetic resonance and 13C, 57Fe electron nuclear double-resonance spectroscopies reveals that it contains an organometallic center in which the 5′ carbon of a SAM-derived deoxyadenosyl moiety forms a bond with the unique iron site of the [4Fe-4S] cluster. Discovery of this intermediate extends the list of enzymatic bioorganometallic centers to the radical SAM enzymes, the largest enzyme superfamily known, and reveals intriguing parallels to B12 radical enzymes.

Original languageEnglish (US)
Pages (from-to)822-825
Number of pages4
JournalScience
Volume352
Issue number6287
DOIs
StatePublished - May 13 2016

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Metalloproteins: Radical SAM catalysis via an organometallic intermediate with an Fe-[5′-C]-deoxyadenosyl bond'. Together they form a unique fingerprint.

Cite this