Coenzyme M reductase

a yellow, water-soluble compound, was first extracted from boiled cells of methanogenic bacteria, a discovery which Wolfe (19) has credited to J. LeGall. Its isolation was first reported by Gunsalus and Wolfe (83). The cofactor has a Soret band in the visible region at 430 nm. Functionally F430 is a prosthetic group of the methylreductase system (24, 84). It is also found in the free state in cell extracts (85). 

Albracht et al. (90) have observed an EPR spectrum from whole cells of M. thermoautotrophicum (Fig. 13) which appears to arise from protein-bound F430. The same type of spectrum was also observed in purified methyl-CoM reductase. The paramagnetic species on whole cells was only partially reduced by treatment with hydrogen and was unaffected by carbon monoxide. Gel filtration showed it to be part of a soluble protein. The spectrum was somewhat broadened by substitution 

F430 is required for the activity of the methylreductase system, which catalyzes the reduction of the methyl group of methyl-CoM, i.e., 2-(methylthio)ethanesulfonate, to methane  

This is a complex process, involving the deazaflavin-reducing hydrog-enase and other proteins, provisionally named factors A-2. A-3, and C (19). The system requires initial activation by ATP before the reaction can proceed (87). Component C consists of two each of three protein subunits of 68,45, and 38.5 kDa and contains two molecules of F430 per molecule, as well as stoichiometric amounts of coenzyme M (91). F430 appears to be tightly but noncovalently bound to the enzyme. 

The exact role of the nickel of F430 in methane formation is not clear at present. Analogy with the cobalamins, and the observation of an EPR-detectable reduced state, might suggest that it is involved in either methyl group transfer, reduction, or both. 

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Methyl-coenzyme M reductase participates in the conversion of CO2 to CH4 and contains 6-coordinate nickel(II) in a highly hydrogenated and highly flexible porphyrin system. This flexibility is believed to allow sufficient distortion of the octahedral ligand field to produce low-spin Ni" (Fig. 27.7) which facilitates the formation of a Ni -CHs intermediate. 

Methyl coenzyme M reductase plays a key role in the production of methane in archaea. It catalyzes the reduction of methyl-coenzyme M with coenzyme B to produce methane and the heterodisulfide (Figure 3.35). The enzyme is an a2P2Y2 hexamer, embedded between two molecules of the nickel-porphinoid F jg and the reaction sequence has been delineated (Ermler et al. 1997). The heterodisulfide is reduced to the sulfides HS-CoB and HS-CoM by a reductase that has been characterized in Methanosarcina thermoph-ila, and involves low-potential hemes, [Fe4S4] clusters, and a membrane-bound metha-nophenazine that contains an isoprenoid chain linked by an ether bond to phenazine (Murakami et al. 2001). 

Ermler U, W Grabarse, S Shima, M Goubeaud, RK Thauer (1997) Crystal structure of methyl-coenzyme M reductase the key enzyme of biological methane formation. Science 278 1457-1462. 

Hallam SJ, PR Girguis, CM Preston, PM Richardson, EF DeLong (2003) Identification of methyl coenzyme M reductase A (merA) genes associated with methane-oxidizing archaea. Appl Environ Microbiol 69 5483-5491. 

A handbook on inorganic and coordination chemistry of porphyrins has been published.1765 Factor F430 is the nickel-hydrocorphinoid group of the enzyme methyl coenzyme M reductase.47,48 The mystery of this particular metalloprotein is one of the major reasons for the development of Ni11-porhyrin coordination chemistry, although not the only one. 

Each catalytic center of methyl coenzyme M reductase, (MCR), contains a yellow chromophore factor F430.4 The structure of Ni-F430 determined by the crystallographic analysis and the proposed mechanism of MCR is shown in Scheme 10.47... 

Similar to porphyrin systems, Ni1 complexes with macrocyclic N4 ligands (in particular of the cyclam type) have been considered particularly instructive with respect to the chemistry of the active site of methyl coenzyme M reductase. In most cases, Ni1 species are produced by... 

C. Finazzo, J. Harmer, B. Jaun, E.C. Duin, F. Mahlert, R.K. Thauer, S. Van Doorslaer and A. Schweiger, Characterization of the MCRred2 form of methyl-coenzyme M reductase A pulse EPR and ENDOR study, J. Biol. Inorg. Chem., 2003, 8, 586. 

Grabarse WG, Mahlert F, Shima S, et al. 2000. Comparison of three methyl-coenzyme M reductases from phylogenetically distant organisms unusual amino acid modification, conservation and adaptation. J Mol Biol 303 329 4. 

Corphin is the F-430 cofactor found in methyl-coenzyme M reductase, a nickel-containing enzyme that participates in the conversion of carbon dioxide to methane in methanogenic bacteria. The nickel ion in F-430 is coordinated by the tetrahydrocorphin ligand, which contains structural elements of both porphyrins and corrins. 

A tetrapyrrole (related to porphyrins and corrins) containing a nickel ion. This cofactor, corphin, is a crucial component of methyl-coenzyme M reductase, a bacterial enzyme participating in the formation of methane. 

Methylbenzene halogen complex of, 3 122 iodine monochloridecomplese, 3 109 Methylchlorosilanes hydrolysis, 42 149-150, 157 pyrolysis products of, 7 356-363 Methylcobalamin, 19 151, 152 Methyl-coenzyme M reductase, 32 323-325 EPR spectra, 32 323, 325 F43 and, 32 323-324 function, 32 324-325 Methyl-CoM reductase, 32 329 Methyl cyanide, osmium carbonyl complexes, reaction, 30 198-201 Methylcyclophosphazene salts, 21 70 synthesis, 21 109... 

Methyl-S-coenzyme-M reductases, 40 342-343 1 -Methyl-2,4,6-triaminocyclohexane, cobalt(III) hexaamines, 35 143-144 2-Methyl-1,2,3-triaminopropane, cobalt(III) hexaamines, 35 142... 

Currently, Ni(I) macrocyclic complexes have attracted much attention. This is because Ni(II) tetraaza macrocyclic complexes catalyze the electrochemical reduction of C02 and alkyl halides, and it is proposed that the Ni(I) species are involved in such reactions (1,2, 76-79, 82, 124-126). Furthermore, F430, a Ni(II) hydrocorphinoid complex, is a prosthetic group of methyl coenzyme M reductase that catalyzes the reductive cleavage of S-methyl coenzyme M to methane in the final stage of C02 reduction to methane (127-130). An EPR signal detected in whole cells of Methanobacterium thermoautotrophicum has been attributed to an Ni(I) form of F430 in intact active enzyme (131,132). 

Figure 16-28 Proposed mechanism of action of the methane-forming coenzyme M reductase. Based on the crystal structure.

Coenzyme A persulfide 790 Coenzyme A transferases 662 Coenzyme 788 Coenzyme M 813s, 814, 815 Coenzyme M reductase mechanism of 881 scheme 880... 

Several macrocyclic ligands are shown in Figure 2. The porphyrin and corrin ring systems are well known, the latter for the cobalt-containing vitamin Bi2 coenzymes. Of more recent interest are the hydroporphyrins. Siroheme (an isobacteriochlorin) is the prosthetic group of the sulfite and nitrite reductases which catalyze the six-electron reductions of sulfite and nitrite to H2S and NH3 respectively. The demetallated form of siroheme, sirohydrochlorin, is an intermediate in the biosynthesis of vitamin Bi2, and so links the porphyrin and corrin macrocycles. Factor 430 is a tetrahydroporphyrin, and as its nickel complex is the prosthetic group of methyl coenzyme M reductase. F430 shows structural similarities to both siroheme and corrin. 

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