Cofactor M reductase

In the case of the DMSO reductase family, as pointed out above, the metal centre is bound to two molecules of the cofactor. DMSO reductase itself catalyses the reduction of dimethylsulfoxide to dimethylsulfide with incorporation of the oxygen atom of DMSO into water. The active site of the oxidized enzyme is an L2MoVI0(0-Ser) centre, which, upon reduction, loses the M=0 ligand to give a L2MoIV(0-Ser) centre. In the catalytic... 

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. 

Ni -F43o reacting directly with MeS-CoM before/after the substrate activation, the role of the thiol cofactor HS-HTP, and the reason(s) for the enzyme specifically directing the C-S bond cleavage to the Me-S bond of Me-CoM are the principal questions to be resolved to understand how the enzyme methyl coenzyme M reductase fimctions. 

Methyl-coenzyme M reductase (MCR) catalyses the reaction of methyl-coenzyme M (H3C-SC0M) and coenzyme B (HS-CoB) to methane and the corresponding disulfide CoM-S-S-CoB. This unique reaction proceeds under strictly anaerobic conditions in the presence of the cofactor F430, also-called factor F430, see Figure 4.10. ... 

Coenzyme F430, the hydrocorphinoid nickel(II) complex (Fig. 3) belongs to the unique group of coenzymes mediating the reduction of C02 to methane in methanogenic bacteria [8,9]. As a cofactor of methylcoenzyme M reductase it is involved in the reductive cleavage of S-methyl coenzyme M to coenzyme M and methane, an exergonic step coupled to the synthesis of ATP. 

The terminal step in methane generation by several methanogenic organisms, of which the best studied is the archaeon Methanobacterium thermoautotrophicum, is catalyzed by the enzyme S-methyl coenzyme M reductase (methylreductase, EC 1.8.-.-). This enzyme contains a macrocyclic tetrapyrrole-derived cofactor, F430, at the active site coordinating Ni(II) in the resting state. A Ni(I) state (Ni1F430) has been proposed as the active form of the cofactor. Extensive mechanistic and spectroscopic studies have been performed on the holoenzyme, isolated cofactor, and various synthetic model compounds. These studies are summarized in... 

Cheesman MR, Ankel Fuchs D, Thauer RK and Thompson AJ (1989) The magnetic properties of the nickel cofactor F430 in the enzyme methyl-coenzyme M reductase of Methanobacterium ther-moautotrophicum. Biochem J 260 613—616. 

For example, incorporation of nickel into carbon monoxide dehydrogenase of Rhodospirillum rubrum requires the prior reduction of an Fe-S cluster. Structural studies of this protein reveal that the added Ni completes a unique [lNi-4Fe-4S] center that is required for activity.Another example of a reductive activation step occurs during NiFe-hydrogenase biosynthesis, perhaps involving participation of the Fe-S cluster in HypD. Yet a third example from the Ni-enzyme literature involves the synthesis of methyl-X-coenzyme M reductase, a methanogen enzyme that contains the Ni-tetrapyrrole cofactor F43q. Formation of active enzyme requires both the reduction of Ni + to NF+ and reduction of a C=N bond in the organic macrocycle. 

Nickel occurs as a cofactor in four enzymes known to date (Walsh and Orme-Johnson, 1987). Ureases from plant and animal sources use two Ni atoms as Lewis acids, a role more typical of Zn. In the other three enzymes, all bacterial. Ni is redox active. In methyl coenzyme M reductase of methanogenic bacteria, Ni is found in a tetrapyrrole (factor F430) and cycles between Ni(ll) and Ni(l). Many bacteria contain Ni-dependent hydroge-nase(s) and methanogenic and acetogenic bacteria have a specific Ni-containing CO... 

The nickel-containing factor F 430 (134) provides an example of how nature exploits the reactivity of organometallic compounds, as is the case with vitamin B12. Factor F 430 (134) plays a key role as cofactor for the coenzyme M reductase of primitive methanogenic bacteria in the formation of methane from 2-(methylthio)-ethanesulfonate (86). The structural elucidation of factor F 430 (134) is based on a combination of classical spectroscopic methods, chemical degradation, and biosynthetic studies with C-labelled precursors 83a,b). These biosynthetic investigations will be addressed in section 8.2. Chemical degradation products obtained by ozonolysis of factor F 430 (134) allowed the determination of the absolute configuration by comparison with reference compounds derived from chlorophyll a (2) and vitamin B12 (4) 83a,b). 

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