On the mechanism of methyl-coenzyme M reductase

Abstract

Methyl-coenzyme M reductase (MCR) catalyzes the reaction of methyl-coenzyme M (CH₃–SCoM) and coenzyme B (HS–CoB) to methane and the corresponding heterodisulfide CoM–S–S–CoB. This unique reaction proceeds under strictly anaerobic conditions in the presence of coenzyme F₄₃₀, a Ni-porphinoid. MCR is a large (αβγ)₂ heterohexameric protein complex containing two 50 Å long active sites channels. Coenzyme F₄₃₀ is embedded at the channel bottom and the substrates CH₃–SCoM and HS–CoB bind in front of F₄₃₀ into a solvent free and hydrophobic channel segment. Two principally different catalytic mechanisms are currently discussed. Mechanism I is based on a nucleophilic attack of Ni(I) onto the methyl group of CH₃–SCoM yielding methyl–Ni(III) and mechanism II on an attack of Ni(I) onto the thioether sulfur of CH₃–SCoM generating a Ni(II)–SCoM intermediate. Both mechanisms are discussed in the light of a large number of data collected about MCR over the last twenty years.