title: A selenium-based click AdoMet analogue for versatile substrate labeling with wild-type protein methyltransferases.
abstract: Protein methylation is catalyzed by S-adenosyl-L-methionine-dependent protein methyltransferases (MTases), and this posttranslational modification serves diverse cellular functions. Some MTases seem to exhibit broad substrate specificities and comprehensive methods for target profiling are needed. Here we report the synthesis of a new AdoMet analogue for enzymatic transfer of a small propargyl group and labeling of modified proteins through copper-catalyzed azide-alkyne cycloaddition (CuAAC). Replacement of sulfur by selenium strongly enhanced the stability of the progargylic cofactor, leading, in combination with better activation by the selenonium center, to higher enzymatic reactivity. A broad spectrum of wild-type protein MTases acting on lysine, arginine, and glutamine residues accept this cofactor and modified substrates can be efficiently labeled by CuAAC click chemistry.
authors.affiliation: Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52056 Aachen, Germany.
authors.forename: Sophie
authors.initials: S
authors.lastname: Willnow
authors.forename: Michael
authors.initials: M
authors.lastname: Martin
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
authors.forename: Elmar
authors.initials: E
authors.lastname: Weinhold
mesh_terms: D057930:Click Chemistry / Q000379:methods; D011496:Protein Methyltransferases / Q000737:chemistry* / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D012643:Selenium / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012436:S-Adenosylmethionine; D011496:Protein Methyltransferases; D012643:Selenium