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Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase.
- Source :
-
Science (New York, N.Y.) [Science] 2016 Mar 18; Vol. 351 (6279), pp. 1320-3. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016, American Association for the Advancement of Science.)
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 351
- Issue :
- 6279
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 26989252
- Full Text :
- https://doi.org/10.1126/science.aad8995