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

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.
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Science, American Association for the Advancement of Science, 2016, 351 (6279), pp.1320-1323. 〈10.1126/science.aad8995〉
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http://hal.univ-grenoble-alpes.fr/hal-01297885
Contributeur : Frank Thomas <>
Soumis le : mardi 5 avril 2016 - 10:02:36
Dernière modification le : jeudi 11 janvier 2018 - 06:23:02

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G. Sicoli, J.-M. Mouesca, Laura Zeppieri, Patricia Amara, Lydie Martin, et al.. Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase. Science, American Association for the Advancement of Science, 2016, 351 (6279), pp.1320-1323. 〈10.1126/science.aad8995〉. 〈hal-01297885〉

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