Crystal Structure of Methyl-Coenzyme M Reductase: The Key Enzyme of Biological Methane Formation

• Published in: Science (American Association for the Advancement of Science) 1997-11, Vol.278 (5342), p.1457-1462
• Main Authors: Ermler, Ulrich, Grabarse, Wolfgang, Shima, Seigo, Goubeaud, Marcel, Thauer, Rudolf K.
• Format: Article
• Language: English
• Subjects: Active sites; Analytical, structural and metabolic biochemistry; Atoms; Binding Sites; Biological and medical sciences; Catalysis; Coenzymes; Coenzymes - chemistry; Coenzymes - metabolism; Crystallography, X-Ray; Crystals; Disulfides - chemistry; Disulfides - metabolism; Enzymes; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Hydrogen - metabolism; Hydrogen Bonding; Ligands; Mesna - analogs & derivatives; Mesna - chemistry; Mesna - metabolism; Metalloporphyrins - chemistry; Metalloporphyrins - metabolism; Methane; Methane - metabolism; Methanobacterium - enzymology; Models, Molecular; Molecules; Nickel - chemistry; Nickel - metabolism; Oxidation-Reduction; Oxidoreductases; Oxidoreductases - chemistry; Oxidoreductases - metabolism; Oxygen; Phosphothreonine - analogs & derivatives; Phosphothreonine - chemistry; Phosphothreonine - metabolism; Protein Conformation; Protein Folding; Protein Structure, Secondary; Scientific Concepts; Sulfonates; Sulfur; Thiols
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.278.5342.1457

Methyl-coenzyme M reductase (MCR), the enzyme responsible for the microbial formation of methane, is a 300-kilodalton protein organized as a hexamer in an $\alpha_2\beta_2\gamma_2$ arrangement. The crystal structure of the enzyme from Methanobacterium thermoautotrophicum, determined at 1.45 angstrom resolution for the inactive enzyme state MCR$_{ox1-silent}$, reveals that two molecules of the nickel porphinoid coenzyme F$_{430}$ are embedded between the subunits α, α′, β, and γ and α′, α, β′, and γ′, forming two identical active sites. Each site is accessible for the substrate methyl-coenzyme M through a narrow channel locked after binding of the second substrate coenzyme B. Together with a second structurally characterized enzyme state (MCR$_{silent}$) containing the heterodisulfide of coenzymes M and B, a reaction mechanism is proposed that uses a radical intermediate and a nickel organic compound.