Biochemistry of Methyl-Coenzyme M Reductase: The Nickel Metalloenzyme that Catalyzes the Final Step in Synthesis and the First Step in Anaerobic Oxidation of the Greenhouse Gas Methane - The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment - page 123

Abstract Methane, the major component of natural gas, has been in use in human
civilization since ancient times as a source of fuel and light. Methanogens
are responsible for synthesis of most of the methane found on Earth. The enzyme
responsible for catalyzing the chemical step of methanogenesis is methyl-
coenzyme M reductase (MCR), a nickel enzyme that contains a tetrapyrrole
cofactor called coenzyme F 430 , which can traverse the Ni(I), (II), and (III) oxidation
states. MCR and methanogens are also involved in anaerobic methane oxidation.
This review describes structural, kinetic, and computational studies aimed at
elucidating the mechanism of MCR. Such studies are expected to impact the
many ramifications of methane in our society and environment, including energy
production and greenhouse gas warming.

Keywords F 430 • methane oxidation • methanogenesis • nickel • tetrapyrrole

Please cite as: Met. Ions Life Sci . 14 (2014) 125-145

1 Introduction

1.1 Nickel Enzymes Involved in Metabolism of Environment-
and Energy-Relevant Gases

Methyl-coenzyme M reductase (MCR) is one of the eight known Ni enzymes
that catalyze the utilization and/or production of gases (methane, CO, CO 2 ,H 2 ,
ammonia, and O 2 ) that play important roles in the global biological carbon, nitrogen,
and oxygen cycles [ 1 ]. While MCR is involved in generating and metabolizing
methane, CO dehydrogenase (CODH) catalyzes the two-electron interconversion of
CO and CO 2 , and acetyl-CoA synthase (ACS) promotes the synthesis of acetyl-CoA
from CO and a methyl group and coenzyme A (CoA). Ni acireductone dioxygenase
facilitates the production of CO/formate, hydrogenase the generation/utilization of
hydrogen gas, urease the production of ammonia, and superoxide dismutase (SOD)
the dismutation of two molecules of superoxide into hydrogen peroxide and O 2 .
Among these enzymes, the Ni sites exhibit extreme plasticity in terms of metal
coordination and oxidation-reduction potentials. For example, the Ni center in
CODH is part of an FeS cluster, the proximal Ni in ACS appears to shift between
tetrahedral and square planar while the distal Ni resembles the planar SOD active
site which ligates Ni with the sulfur atoms of two Cys residues and two peptide
backbone nitrogens, and the Ni in MCR is ligated by the planar nitrogens of a
tetrapyrrole ring that switches among octahedral, square pyramidal and planar
geometries. Furthermore, the Ni centers among the various enzymes must be able
to catalyze redox processes with potentials that span from +890 mV to 160 mV

[ 2 ], while in MCR, CODH, and ACS, it must be able to reach potentials as low
as 600 mV [ 3 ]; thus, Ni centers in proteins perform redox chemistry over a

potential range of ~1.5 V!