On the mechanism of methyl-coenzyme M reductase

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 (alphabetagamma)2 heterohexameric protein complex containing two 50 A 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.