Radical S -Adenosyl- l -Methionine Enzyme PylB: A C-Centered Radical to Convert l -Lysine into (3 R )-3-Methyl- d -Ornithine - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of the American Chemical Society Année : 2024

Radical S -Adenosyl- l -Methionine Enzyme PylB: A C-Centered Radical to Convert l -Lysine into (3 R )-3-Methyl- d -Ornithine

Mickael Cherrier
Philip Tatham
Patricia Amara
Yvain Nicolet

Résumé

PylB is a radical S-adenosyl-l-methionine (SAM) enzyme predicted to convert l-lysine into (3R)-3-methyl-d-ornithine, a precursor in the biosynthesis of the 22nd proteogenic amino acid pyrrolysine. This protein highly resembles that of the radical SAM tyrosine and tryptophan lyases, which activate their substrate by abstracting a H atom from the amino-nitrogen position. Here, combining in vitro assays, analytical methods, electron paramagnetic resonance spectroscopy, and theoretical methods, we demonstrated that instead, PylB activates its substrate by abstracting a H atom from the Cγ position of L-lysine to afford the radical-based β-scission. Strikingly, we also showed that PylB catalyzes the reverse reaction, converting (3R)-3-methyl-d-ornithine into L-lysine and using catalytic amounts of the 5'-deoxyadenosyl radical. Finally, we identified significant in vitro production of 5'-thioadenosine, an unexpected shunt product that we propose to result from the quenching of the 5'-deoxyadenosyl radical species by the nearby [Fe4S4] cluster.
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Dates et versions

hal-04496232 , version 1 (08-03-2024)

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Feryel Soualmia, Mickael Cherrier, Timothée Chauviré, Mickaël Mauger, Philip Tatham, et al.. Radical S -Adenosyl- l -Methionine Enzyme PylB: A C-Centered Radical to Convert l -Lysine into (3 R )-3-Methyl- d -Ornithine. Journal of the American Chemical Society, 2024, 146 (10), pp.6493-6505. ⟨10.1021/jacs.3c03747⟩. ⟨hal-04496232⟩
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