Related Experiment Video
Updated: Nov 21, 2025

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Structural basis for non-radical catalysis by TsrM, a radical SAM methylase
Hayley L Knox1, Percival Yang-Ting Chen2,3, Anthony J Blaszczyk4,5
1Department of Chemistry, Pennsylvania State University, University Park, PA, USA.
Abstract:
Tryptophan 2C methyltransferase (TsrM) methylates C2 of the indole ring of L-tryptophan during biosynthesis of the quinaldic acid moiety of thiostrepton. TsrM is annotated as a cobalamin-dependent radical S-adenosylmethionine (SAM) methylase; however, TsrM does not reductively cleave SAM to the universal 5'-deoxyadenosyl 5'-radical intermediate, a hallmark of radical SAM (RS) enzymes. Herein, we report structures of TsrM from Kitasatospora setae, which are the first structures of a cobalamin-dependent radical SAM methylase. Unexpectedly, the structures show an essential arginine residue that resides in the proximal coordination sphere of the cobalamin cofactor, and a [4Fe-4S] cluster that is ligated by a glutamyl residue and three cysteines in a canonical CXXXCXXC RS motif. Structures in the presence of substrates suggest a substrate-assisted mechanism of catalysis, wherein the carboxylate group of SAM serves as a general base to deprotonate N1 of the tryptophan substrate, facilitating the formation of a C2 carbanion.
More Related Videos
17:12Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry CCMS
Published on: December 20, 2010
09:37Imine Metathesis by Silica-Supported Catalysts Using the Methodology of Surface Organometallic Chemistry
Published on: October 18, 2019
Related Concept Videos
Radical Reactivity: Overview
Radical Reactivity: Steric Effects
Along with electronic...
Radical Reactivity: Nucleophilic Radicals
Radical Reactivity: Intramolecular vs Intermolecular
Radical Reactivity: Electrophilic Radicals
Radical Substitution: Hydrogenolysis of Alkyl Halides with Tributyltin Hydride
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation reactions,...