Max-Planck researchers unravel the structure of the methane forming enzyme
A team of the Max-Planck Institutes from Frankfurt and Marburg has recently determined the structure of methyl-coenzyme M reductase, a key enzyme of methanogenesis that catalyzes a highly complex chemical reaction namely the reduction of a thioether to a hydrocarbon.
Methanogenesis is only carried out by a group of strictly anaerobic microbes called methanogens which use the formation of methane for the purpose of cellular energy generation. Within the microbial ecosystem methanogens participate in the final step of anoxic decomposition of complex organic materials thereby producing about 109 tons of methane per year. The generated methane is either remetabolized by methanotrophic bacteria or escapes to the atmosphere as a potent greenhouse gas. All methanogens are dependent on the enzyme methyl-CoM reductase, a protein complex of 300 kDa size. Its crystal structure was solved to a resolution of 1.45 E which represents the highest resolution for biological macromolecules of that size so far.
Nature has evolved with methyl-coenzyme M reductase a remarkable enzyme composed of six subunits forming a heterohexamer in an (a,_,c)2 arrangement. Three unusual coenzymes are embedded in a 30 E long channel between the subunits. Of particular interest is the binding of coenzyme F430, a Ni-porphinoid which exclusively occurs in this enzyme. As substrates the enzyme binds methyl-coenzyme M (methyl-thioethane sulfonate) and coenzyme B (7-thioheptanoyl threoninephosphate). The highly resolved crystal structure allows a description of the binding modes of these 3exotic2 coenzymes within the protein on an atomic ground.
The biochemical reaction of methyl-coenzyme M reductase proceeds by reducing of methyl-coenzyme M to methane and by oxidizing of coenzyme M and coenzyme B to the corresponding heterodisulfide. From the viewpoint of a synthetic chemist this type of thioether cleavage is extremely difficult to perform, nearly impossible in aqueous solutions, and has so far no equivalent in the organic chemistry. The enzyme circumvents the problems in aqueous solution by wrapping the reaction into the protein. The active site is coated by hydrophobic, aromatic side chains and completely inaccessible for bulk solvent. The arrangement of the coenzymes suggests that the nickel atom of coenzyme F430 is involved in the reaction by forming a short-living Ni-CH3, metal-organic compound rarely found in biological systems. The structure was solved in two different enzyme states which ressemble the coenzyme binding before and after reduction. When comparing the two enzyme states coenzyme M moves more about 4 E and thus provides a dynamic impression of the reaction.In summary, the structure at 1.45 E resolution provided us with new insights with respect to the general design and the detailed enzymatic mechanism of such a complex biochemical reaction. Moreover, this structure can serve as reference point, to interprete more reliable biochemical and spectroscopic observations and to characterize the structures of other enzyme states in the future.
Journal
Science