Crystallographic snapshots of a B-12-dependent radical SAM methyltransferase

Article

关键词: DEPENDENT METHIONINE SYNTHASE;    COENZYME-M REDUCTASE;    S-ADENOSYLMETHIONINE;    CRYSTAL-STRUCTURE;    ENZYME;    COBALAMIN;    BIOSYNTHESIS;    MODEL;    METHYLATION;    IRON;   

DOI  :  10.1038/s41586-021-04355-9

来源: SCIE

【 摘 要 】

By catalysing the microbial formation of methane, methyl-coenzyme M reductase has a central role in the global levels of this greenhouse gas(1,2). The activity of methyl-coenzyme M reductase is profoundly affected by several unique post-translational modifications(3-6), such as a unique C-methylation reaction catalysed by methanogenesis marker protein 10 (Mmp10), a radical S-adenosyl-l-methionine (SAM) enzyme(7,8). Here we report the spectroscopic investigation and atomic resolution structure of Mmp10 from Methanosarcina acetivorans, a unique B-12 (cobalamin)-dependent radical SAM enzyme(9). The structure of Mmp10 reveals a unique enzyme architecture with four metallic centres and critical structural features involved in the control of catalysis. In addition, the structure of the enzyme-substrate complex offers a glimpse into a B-12-dependent radical SAM enzyme in a precatalytic state. By combining electron paramagnetic resonance spectroscopy, structural biology and biochemistry, our study illuminates the mechanism by which the emerging superfamily of B-12-dependent radical SAM enzymes catalyse chemically challenging alkylation reactions and identifies distinctive active site rearrangements to provide a structural rationale for the dual use of the SAM cofactor for radical and nucleophilic chemistry.

【 授权许可】

Free