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Crystal Structure of Tryptophan Lyase (NosL): Evidence for Radical Formation at the Amino Group of Tryptophan
Author(s) -
Nicolet Yvain,
Zeppieri Laura,
Amara Patricia,
FontecillaCamps Juan C.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201407320
Subject(s) - chemistry , tryptophan , stereochemistry , indole test , amino acid , cleavage (geology) , crystal structure , organic chemistry , biochemistry , geotechnical engineering , fracture (geology) , engineering
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 CαCβ 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 CαCβ 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.