Crystallographic snapshots of a B12-dependent radical SAM methyltransferase - Archive ouverte HAL Access content directly
Journal Articles Nature Year : 2022

Crystallographic snapshots of a B12-dependent radical SAM methyltransferase

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Abstract

Abstract 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.
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Dates and versions

hal-03808863 , version 1 (21-10-2022)

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Cameron Fyfe, Noelia Bernardo-García, Laura Fradale, Stéphane Grimaldi, Alain Guillot, et al.. Crystallographic snapshots of a B12-dependent radical SAM methyltransferase. Nature, 2022, 602 (7896), pp.336-342. ⟨10.1038/s41586-021-04355-9⟩. ⟨hal-03808863⟩
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