U.S. Department of Energy Office of Scientific and Technical Information
Nickel–Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long-Range Electron Transfer
Journal Article·· Journal of the American Chemical Society
Methyl-coenzyme M reductase (MCR) catalyzes both the synthesis and the anaerobic oxidation of methane (AOM). Its catalytic site contains Ni at the core of cofactor F430. The Ni ion, in its low-valent Ni(I) state, lights the fuse leading to homolysis of the C–S bond of methyl-coenzyme M (methyl-SCoM) to generate a methyl radical, which abstracts a hydrogen atom from coenzyme B (HSCoB) to generate methane and the mixed disulfide CoMSSCoB. Direct reversal of this reaction activates methane to initiate anaerobic methane oxidation. On the basis of the crystal structures, which reveal a Ni–thiol interaction between Ni(II)–MCR and inhibitor CoMSH, a Ni(I)–thioether complex with substrate methyl-SCoM has been transposed to canonical MCR mechanisms. Similarly, a Ni(I)–disulfide with CoMSSCoB is proposed for the reverse reaction. However, this Ni(I)–sulfur interaction poses a conundrum for the proposed hydrogen-atom abstraction reaction because the >6 Å distance between the thiol group of SCoB and the thiol of SCoM observed in the structures appears to be too long for such a reaction. The spectroscopic, kinetic, structural, and computational studies described here establish that both methyl-SCoM and CoMSSCoB bind to the active Ni(I) state of MCR through their sulfonate groups, forming a hexacoordinate Ni(I)–N/O complex, not Ni(I)–S. These studies rule out direct Ni(I)–sulfur interactions in both substrate-bound states. As a solution to the mechanistic conundrum, we propose that both the forward and the reverse MCR reactions emanate through long-range electron transfer from the Ni(I)–sulfonate complexes with methyl-SCoM and CoMSSCoB, respectively.
Patwardhan, Anjali, et al. "Nickel–Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long-Range Electron Transfer." Journal of the American Chemical Society, vol. 143, no. 14, Mar. 2021. https://doi.org/10.1021/jacs.1c01086
Patwardhan, Anjali, Sarangi, Ritimukta, Ginovska, Bojana, Raugei, Simone, & Ragsdale, Stephen W. (2021). Nickel–Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long-Range Electron Transfer. Journal of the American Chemical Society, 143(14). https://doi.org/10.1021/jacs.1c01086
Patwardhan, Anjali, Sarangi, Ritimukta, Ginovska, Bojana, et al., "Nickel–Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long-Range Electron Transfer," Journal of the American Chemical Society 143, no. 14 (2021), https://doi.org/10.1021/jacs.1c01086
@article{osti_1797985,
author = {Patwardhan, Anjali and Sarangi, Ritimukta and Ginovska, Bojana and Raugei, Simone and Ragsdale, Stephen W.},
title = {Nickel–Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long-Range Electron Transfer},
annote = {Methyl-coenzyme M reductase (MCR) catalyzes both the synthesis and the anaerobic oxidation of methane (AOM). Its catalytic site contains Ni at the core of cofactor F430. The Ni ion, in its low-valent Ni(I) state, lights the fuse leading to homolysis of the C–S bond of methyl-coenzyme M (methyl-SCoM) to generate a methyl radical, which abstracts a hydrogen atom from coenzyme B (HSCoB) to generate methane and the mixed disulfide CoMSSCoB. Direct reversal of this reaction activates methane to initiate anaerobic methane oxidation. On the basis of the crystal structures, which reveal a Ni–thiol interaction between Ni(II)–MCR and inhibitor CoMSH, a Ni(I)–thioether complex with substrate methyl-SCoM has been transposed to canonical MCR mechanisms. Similarly, a Ni(I)–disulfide with CoMSSCoB is proposed for the reverse reaction. However, this Ni(I)–sulfur interaction poses a conundrum for the proposed hydrogen-atom abstraction reaction because the >6 Å distance between the thiol group of SCoB and the thiol of SCoM observed in the structures appears to be too long for such a reaction. The spectroscopic, kinetic, structural, and computational studies described here establish that both methyl-SCoM and CoMSSCoB bind to the active Ni(I) state of MCR through their sulfonate groups, forming a hexacoordinate Ni(I)–N/O complex, not Ni(I)–S. These studies rule out direct Ni(I)–sulfur interactions in both substrate-bound states. As a solution to the mechanistic conundrum, we propose that both the forward and the reverse MCR reactions emanate through long-range electron transfer from the Ni(I)–sulfonate complexes with methyl-SCoM and CoMSSCoB, respectively.},
doi = {10.1021/jacs.1c01086},
url = {https://www.osti.gov/biblio/1797985},
journal = {Journal of the American Chemical Society},
issn = {ISSN 0002-7863},
number = {14},
volume = {143},
place = {United States},
publisher = {American Chemical Society (ACS)},
year = {2021},
month = {03}}