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.
Ermler
Ulrich
U
Max-Planck-Institut für Biophysik, Max-von-Laue-Str. 3, D-60438, Frankfurt am Main, Germany. ulrich.ermler@mpibp-frankfurt.mpg.de
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; C023540:factor F430; D010088:Oxidoreductases; C021572:methyl coenzyme M reductase