Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase

G. Sicoli; J.-M. Mouesca; Laura Zeppieri; Patricia Amara; Lydie Martin; A.-L. Barra; Juan-Carlos Fontecilla-Camps; S. Gambarelli; Yvain Nicolet

doi:10.1126/science.aad8995

Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase

G. Sicoli ¹ J.-M. Mouesca ¹ Laura Zeppieri ² Patricia Amara ² Lydie Martin ² A.-L. Barra ³ Juan-Carlos Fontecilla-Camps ² S. Gambarelli ⁴ Yvain Nicolet ²

1 SCIB - UMR E3 - Service de Chimie Inorganique et Biologique

2 IBS - UMR 5075 - Institut de biologie structurale

3 LNCMI - Laboratoire national des champs magnétiques intenses - Grenoble

4 INAC - Institut Nanosciences et Cryogénie

Abstract : The radical S-adenosyl-L-methionine tryptophan lyase NosL converts L-tryptophan into 3-methylindolic acid, which is a precursor in the synthesis of the thiopeptide antibiotic nosiheptide. Using electron paramagnetic resonance spectroscopy and multiple L-tryptophan isotopologues, we trapped and characterized radical intermediates that indicate a carboxyl fragment migration mechanism for NosL. This is in contrast to a proposed fragmentation-recombination mechanism that implied Cα-Cβ bond cleavage of L-tryptophan. Although NosL resembles related tyrosine lyases, subtle substrate motions in its active site are responsible for a fine-tuned radical chemistry, which selects the Cα-C bond for disruption. This mechanism highlights evolutionary adaptation to structural constraints in proteins as a route to alternative enzyme function.

Type de document :

Article dans une revue

Science, American Association for the Advancement of Science, 2016, 351 (6279), pp.1320-1323. 〈10.1126/science.aad8995〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire / Biologie structurale [q-bio.BM]

Liste complète des métadonnées

http://hal.univ-grenoble-alpes.fr/hal-01297885
Contributeur : Frank Thomas <>
Soumis le : mardi 5 avril 2016 - 10:02:36
Dernière modification le : vendredi 9 mars 2018 - 16:36:02

Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase

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Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase

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