Biochemistry of the Methylcoenzyme M Methylreductase System

Abstract

The reduction of 2-(methylthio)ethanesulfonate (CH₃-S-CoM) is catalyzed by the methylreductase, also known as component C. The prosthetic group of component C is a Ni tetrapyrrole. In its active form, the methylreductase can reductively demethylate CH₃-S-CoM by itself using N-7-mercapto-heptanoyl-O ³-phospho-L-theornine (HS-HTP)as a reductant and produce CH₄ and CoM-S-S-HTP, the heterodisulfide of 2-mercaptoethanesulfonate (HS-CoM) and HS-HTP. However, such active preparations of component C are unstable, and “inactive” methylreductase needs other enzymatic fractions as well as ATP. The number of enzymatic fractions needed varies with the nature of the electron donor. When H₂ is used as the sole source of electrons, at least four enzymatic fractions (Al, A2, A3a and A3b) are required in addition to component C. In this complex system, HS-HTP cannot act as the sole source of electrons and still requires the presence of H₂ to reductively reactivate the methylreductase. If H₂ is used in conjunction with substrate amounts of HS-HTP, the requirement for Al is bypassed, indicating that Al is involved in the regeneration of HS-HTP from CoM-S-S-HTP, probably through the F₄₂₀- reducing hydrogenase. If titanium citrate is used as the sole source of electrons, the requirements for H2 and for A3b, which contains the methylviologen hydrogenase, are bypassed. Our current model for the reactivation of the methylreductase proposes that A2 catalyzes an ATP-dependent allosteric modification of A3a, an FeS protein, lowering the mid-point potential of its FeS centers to values enabling it to reduce the nickel atoms in the methylreductase from Ni^II to Ni^I.