Crystal structure of tryptophan lyase (NosL): evidence for radical formation at the amino group of tryptophan - PubMed (original) (raw)

. 2014 Oct 27;53(44):11840-4.

doi: 10.1002/anie.201407320. Epub 2014 Sep 5.

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

Yvain Nicolet et al. Angew Chem Int Ed Engl. 2014.

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.

Keywords: biotransformations; density functional calculations; enzymes; radicals; reaction mechanisms.

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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