Radical S -Adenosyl- l -methionine Tryptophan Lyase (NosL): How the Protein Controls the Carboxyl Radical •CO 2 – Migration - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of the American Chemical Society Année : 2018

Radical S -Adenosyl- l -methionine Tryptophan Lyase (NosL): How the Protein Controls the Carboxyl Radical •CO 2 – Migration

Résumé

The radical S-adenosyl-l-methionine tryptophan lyase uses radical-based chemistry to convert l-tryptophan into 3-methyl-2-indolic acid, a fragment in the biosynthesis of the thiopeptide antibiotic nosiheptide. This complex reaction involves several successive steps corresponding to (i) the activation by a specific hydrogen-atom abstraction, (ii) an unprecedented •CO2- radical migration, (iii) a cyanide fragment release, and (iv) the termination of the radical-based reaction. In vitro study of this reaction is made more difficult because the enzyme produces a significant amount of a shunt product instead of the natural product. Here, using a combination of X-ray crystallography, electron paramagnetic resonance spectroscopy, and quantum and hybrid quantum mechanical/molecular mechanical calculations, we have deciphered the fine mechanism of the key •CO2- radical migration, highlighting how the preorganized active site of the protein tightly controls this reaction.
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Dates et versions

hal-02008403 , version 1 (05-02-2019)

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Patricia Amara, Jean-Marie Mouesca, Maxime Bella, Lydie Martin, Claire Saragaglia, et al.. Radical S -Adenosyl- l -methionine Tryptophan Lyase (NosL): How the Protein Controls the Carboxyl Radical •CO 2 – Migration. Journal of the American Chemical Society, 2018, 140 (48), pp.16661-16668. ⟨10.1021/jacs.8b09142⟩. ⟨hal-02008403⟩
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