Crystal structure of tryptophan lyase (NosL): evidence for radical formation at the amino group of tryptophan.

Abstract : Streptomyces actuosus tryptophan lyase (NosL) is a radical SAM enzyme which catalyzes the synthesis of 3-methyl-2-indolic acid, a precursor in the synthesis of the promising antibiotic nosiheptide. The reaction involves cleavage of the tryptophan Cα-Cβ bond and recombination of the amino-acid-derived -COOH fragment at the indole ring. Reported herein is the 1.8 Å resolution crystal structure of NosL complexed with its substrate. Unexpectedly, only one of the tryptophan amino hydrogen atoms is optimally placed for H abstraction by the SAM-derived 5'-deoxyadenosyl radical. This orientation, in turn, rules out the previously proposed delocalized indole radical as the species which undergoes Cα-Cβ bond cleavage. Instead, stereochemical considerations indicate that the reactive intermediate is a (·)NH tryptophanyl radical. A structure-based amino acid sequence comparison of NosL with the tyrosine lyases ThiH and HydG strongly suggests that an equivalent (·)NH radical operates in the latter enzymes.
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Article dans une revue
Angewandte Chemie (English Edition), John Wiley & Sons, 2014, 53 (44), pp.11840-4
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http://hal.univ-grenoble-alpes.fr/hal-01119795
Contributeur : Frank Thomas <>
Soumis le : mardi 24 février 2015 - 09:50:21
Dernière modification le : jeudi 15 mars 2018 - 01:33:30

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  • HAL Id : hal-01119795, version 1
  • PUBMED : 25196319

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Yvain Nicolet, Laura Zeppieri, Patricia Amara, Juan-Carlos Fontecilla-Camps. Crystal structure of tryptophan lyase (NosL): evidence for radical formation at the amino group of tryptophan.. Angewandte Chemie (English Edition), John Wiley & Sons, 2014, 53 (44), pp.11840-4. 〈hal-01119795〉

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