7QBV

B12-dependent radical SAM methyltransferase, Mmp10 with [4Fe-4S] cluster, cobalamin, and S-adenosyl-L-homocysteine bound.

Summary for 7QBV

• Entry DOI: 10.2210/pdb7qbv/pdb
• Related: 7QBS 7QBT 7QBU
• Descriptor: Methyl coenzyme M reductase-arginine methyltransferase Mmp10, IRON/SULFUR CLUSTER, FE (III) ION, ... (7 entities in total)
• Functional Keywords: radical sam, b12 binding, methyltransferase, sp3 carbon methylation, metal binding protein
• Biological source: Methanosarcina acetivorans
• Total number of polymer chains: 4
• Total formula weight: 200496.51

Authors

Fyfe, C.D.,Chavas, L.M.G.,Legrand, P.,Benjdia, A.,Berteau, O. (deposition date: 2021-11-19, release date: 2022-02-02, Last modification date: 2024-01-31)

Primary citation

Fyfe, C.D.,Bernardo-Garcia, N.,Fradale, L.,Grimaldi, S.,Guillot, A.,Brewee, C.,Chavas, L.M.G.,Legrand, P.,Benjdia, A.,Berteau, O.
Crystallographic snapshots of a B 12 -dependent radical SAM methyltransferase.
Nature, 602:336-342, 2022

PubMed Abstract: By catalysing the microbial formation of methane, methyl-coenzyme M reductase has a central role in the global levels of this greenhouse gas. The activity of methyl-coenzyme M reductase is profoundly affected by several unique post-translational modifications, such as  a unique C-methylation reaction catalysed by methanogenesis marker protein 10 (Mmp10), a radical S-adenosyl-L-methionine (SAM) enzyme. Here we report the spectroscopic investigation and atomic resolution structure of Mmp10 from Methanosarcina acetivorans, a unique B (cobalamin)-dependent radical SAM enzyme. 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-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-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.

PubMed: 35110733
DOI: 10.1038/s41586-021-04355-9

Experimental method

X-RAY DIFFRACTION (2.701 Å)