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Tryptophan Lyase (NosL): A Cornucopia of 5′-Deoxyadenosyl Radical Mediated Transformations

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journal contribution
posted on 18.11.2016, 00:00 by Dhananjay M. Bhandari, Dmytro Fedoseyenko, Tadhg P. Begley
Tryptophan lyase (NosL) is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the formation of 3-methyl-2-indolic acid from l-tryptophan. In this paper, we demonstrate that the 5′-deoxyadenosyl radical is considerably more versatile in its chemistry than previously anticipated: hydrogen atom abstraction from Nα-cyclopropyltryptophan occurs at Cα rather than the amino group with NosL Y90A and replacing the substrate amine with a ketone or an alkene changes the chemistry from hydrogen atom abstraction to double bond addition. In addition, the 5′-deoxyadenosyl radical can add to the [4Fe−4S] cluster and dithionite can be used to trap radicals at the active site.