A Cobalamin‐Dependent Radical SAM Enzyme Catalyzes the Unique Cα‐Methylation of Glutamine in Methyl‐Coenzyme M Reductase. (4th July 2022)

• Record Type: Journal Article
• Authors: Gagsteiger, Jana; Jahn, Sören; Heidinger, Lorenz; Gericke, Lukas; Andexer, Jennifer N.; Friedrich, Thorsten; Loenarz, Christoph; Layer, Gunhild
• Is Part Of: Angewandte Chemie. Volume 134:Number 32(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-04
• Subjects: MCR Modification -- Metalloproteins -- Methanogenesis -- Radical Reactions -- Radical S-Adenosylmethionine; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202204198
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Methyl‐coenzyme M reductase, which is responsible for the production of the greenhouse gas methane during biological methane formation, carries several unique posttranslational amino acid modifications, including a 2‐( S )‐methylglutamine. The enzyme responsible for the Cα ‐methylation of this glutamine is not known. Herein, we identify and characterize a cobalamin‐dependent radical SAM enzyme as the glutamine C‐methyltransferase. The recombinant protein from Methanoculleus thermophilus binds cobalamin in a base‐off, His‐off conformation and contains a single [4Fe‐4S] cluster. The cobalamin cofactor cycles between the methyl‐cob(III)alamin, cob(II)alamin and cob(I)alamin states during catalysis and produces methylated substrate, 5′‐deoxyadenosine and S ‐adenosyl‐l ‐homocysteine in a 1 : 1 : 1 ratio. The newly identified glutamine C‐methyltransferase belongs to the class B radical SAM methyltransferases known to catalyze challenging methylation reactions of sp 3 ‐hybridized carbon atoms. Abstract : The enzyme responsible for the unique Cα ‐methylation of a glutamine residue within methyl‐coenzyme M reductase was identified. Biochemical, spectroscopic and mass spectrometric characterization clearly classify the newly identified glutamine C‐methyltransferase as a cobalamin‐dependent radical SAM enzyme and, thus, as a new member of the class B radical SAM methyltransferase family.