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

• Autores: Masaki Horitani, Krista Shisler, William E. Broderick
• Localización: Science, ISSN 0036-8075, Vol. 352, Nº 6287, 2016, págs. 822-825
• Idioma: inglés
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• Resumen

  • 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.