CRYSTAL-STRUCTURE OF METHYL COENZYME M-REDUCTASE - THE KEY ENZYME OF BIOLOGICAL METHANE FORMATION

Methyl-coenzyme M reductase (MCR), the enzyme responsible for the micr obial formation of methane, is a 300-kilodalton protein organized as a hexamer in an alpha(2) beta(2) gamma(2) arrangement. The crystal stru cture of the enzyme from Methanobacterium thermoautotrophicum, determi ned at 1.45 angstrom resolution for the inactive enzyme state MCRox1-s ilent, reveals that two molecules of the nickel porphinoid coenzyme F- 430 are embedded between the subunits alpha,alpha',beta, and gamma and alpha',alpha,beta', and gamma', forming two identical active sites. E ach site is accessible for the substrate methyl-coenzyme M through a n arrow channel locked after binding of the second substrate coenzyme B. Together with a second structurally characterized enzyme state (MCRsi lent) containing the heterodisulfide of coenzymes M and B, a reaction mechanism is proposed that uses a radical intermediate and a nickel or ganic compound.