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

Abstract

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 α 2 β 2 γ 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.