Structure reveals why radical enzyme isn’t radical

Abstract

The family of enzymes known as the radical S -adenosyl- l -methionine (SAM) enzymes catalyzes thousands of reactions across biology. Most radical SAM enzymes work via a mechanism in which cleavage of SAM forms a radical. But tryptophan 2C methyltransferase (TsrM), which catalyzes the addition of a methyl group to the indole of l -tryptophan in the synthesis of the antibiotic thiostrepton, isn’t a typical radical SAM enzyme. It uses SAM as a substrate but doesn’t form a radical. Squire J. Booker and Hayley L. Knox of Pennsylvania State University, Catherine L. Drennan and Percival Yang-Ting Chen of the Massachusetts Institute of Technology, and coworkers report structures of TsrM from the bacterium Kitasatospora setae that may help explain the enzyme’s anomalous behavior ( Nat. Chem. Biol. 2021, DOI: 10.1038/s41589-020-00717-y ). The team proposes that SAM plays a dual role in the reaction. It donates a methyl group to the enzyme’s