Abstract
Methyl-coenzyme M reductase (MCR) catalyzes the methane-forming step in methanogenic archaea. The active enzyme harbors the nickel(I) hydrocorphin coenzyme F-430 as a prosthetic group and catalyzes the reversible reduction of methyl-coenzyme M (CH3–S-CoM) with coenzyme B (HS-CoM) to methane and CoM-S–S-CoB. MCR is also involved in anaerobic methane oxidation in reverse of methanogenesis and most probably in the anaerobic oxidation of ethane, propane, and butane. The challenging question is how the unreactive CH3–S thioether bond in methyl-coenzyme M and the even more unreactive C–H bond in methane and the other hydrocarbons are anaerobically cleaved. A key to the answer is the negative redox potential (Eo′) of the Ni(II)F-430/Ni(I)F-430 couple below −600 mV and the radical nature of Ni(I)F-430. However, the negative one-electron redox potential is also the Achilles heel of MCR; it makes the nickel enzyme one of the most O2-sensitive enzymes known to date. Even under physiological conditions, the Ni(I) in MCR is oxidized to the Ni(II) or Ni(III) states, e.g., when in the cells the redox potential (E′) of the CoM-S–S-CoB/HS-CoM and HS-CoB couple (Eo′ = −140 mV) gets too high. Methanogens therefore harbor an enzyme system for the reactivation of inactivated MCR in an ATP-dependent reduction reaction. Purification of active MCR in the Ni(I) oxidation state is very challenging and has been achieved in only a few laboratories. This perspective reviews the function, structure, and properties of MCR, what is known and not known about the catalytic mechanism, how the inactive enzyme is reactivated, and what remains to be discovered.
Highlights
Methyl-coenzyme M reductase (MCR) catalyzes the methaneforming step in methanogenic archaea
Most of the enzymes involved in the biosynthesis of coenzyme M and coenzyme B are unique to methanogenic archaea.[14]
In the beginning of the 2000s, MCR was found in methane-oxidizing anaerobic archaea.[37,38]
Summary
MCR was discovered almost 50 years ago in methanogens and has been intensively studied ever since . The described catalytic mechanism cannot explain, why the two active sites of the α2β2γ2 hexamer are structurally and mechanistically coupled (half-of-the-sites reactivity).[135] It appears from mutation studies published in the last two years that the unique, highly conserved post-translational modifications, thioglycine and 5-methylarginine, in the active site of MCRs are essential only under stress conditions.[127,130] One of the assumptions made in the interpretation of the in vivo genetic results is that MCR catalyzes the growth-ratelimiting step, which is only correct under growth conditions prevailing in the natural environment of the methanogens. There is still a lot to be resolved before we start understanding how MCR and its activation function
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