Download MendeleyCrystal Structure of Tryptophan Lyase (NosL): Evidence for Radical Formation at the Amino Group of Tryptophan.
Nicolet, Y., Zeppieri, L., Amara, P., Fontecilla-Camps, J.C.(2014) Angew Chem Int Ed Engl 53: 11840-11844
- PubMed: 25196319
- DOI: https://doi.org/10.1002/anie.201407320
- Primary Citation of Related Structures:
4R33, 4R34 - PubMed 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?? 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.
Organizational Affiliation:
Metalloproteins Unit, Institut de Biologie Structurale, UMR5075, CEA, CNRS, Université Grenoble-Alpes, 71, avenue des Martyrs, CS 10090, 38044 Grenoble cedex 9 (France). yvain.nicolet@ibs.fr.
