Nickel–Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long-Range Electron Transfer

Methyl-coenzyme M reductase (MCR) catalyzes both the synthesis and anaerobic oxidation of methane (AOM). Its catalytic site contains Ni at core cofactor F430. The ion, in its low-valent Ni(I) state, lights fuse leading to homolysis C–S bond methyl-coenzyme (methyl-SCoM) generate a methyl radical, which abstracts hydrogen atom from coenzyme B (HSCoB) mixed disulfide CoMSSCoB. Direct reversal this reaction activates initiate oxidation. On basis crystal structures, reveal Ni–thiol interaction between Ni(II)–MCR inhibitor CoMSH, Ni(I)–thioether complex with substrate methyl-SCoM has been transposed canonical MCR mechanisms. Similarly, Ni(I)–disulfide CoMSSCoB is proposed for reverse reaction. However, Ni(I)–sulfur poses conundrum hydrogen-atom abstraction because >6 Å distance thiol group SCoB SCoM observed structures appears be too long such spectroscopic, kinetic, structural, computational studies described here establish that bind active state through their sulfonate groups, forming hexacoordinate Ni(I)–N/O complex, not Ni(I)–S. These rule out direct interactions substrate-bound states. As solution mechanistic conundrum, we propose forward reactions emanate long-range electron transfer Ni(I)–sulfonate complexes CoMSSCoB, respectively.