Corrinoid iron-sulfur protein

Corrinoid iron-sulfur protein (CFeSP) purified and characterized acetyl-CoA synthesis reconstituted from CH3-H4 folate, CO, and CoA using purified proteins. ... 

Fig. 11. Active sites and reactions of the bifunctional CODH/ACS. For synthesis of acetyl-CoA, two electrons are transferred from external electron donors to Cluster B of the CODH subunit. Electrons are relayed to Cluster C which reduces CO2 to CO. The CO is proposed to be channeled to Cluster A of the ACS subunit to form a metal-CO adduct that combines with the methyl group of the CFeSP and CoA to form acetyl-CoA. For utilization of acetyl-CoA, these reactions are reversed. The abbreviations are CODH, CO dehydrogenase ACS, acetyl-CoA synthase CFeSP, the corrinoid iron-sulfur protein CoA, Coenzyme A.

Maillard J, W Schumacher, F Vazquez, C Regeard, WR Hagen, C Holliger (2003) Characterization of the corrinoid iron-sulfur protein tetrachloroethene reductive dehalogenase of Dehalobacter restrictus. Appl Environ Microbiol 69 4628-4638. 

The corrinoid iron-sulfur protein from, for example, the anaerobic bacterium Cl. thermoaceticum participates in the Wood pathway for fixation of C02 in acetate biosynthesis. A methyl transferase converts CH3-H4folate and the corrinoid iron-sulfur protein to CH3-corrinoid iron-sulfur protein. The latter protein then transfers the CH3-group to carbon monoxide dehydrogenase. As mentioned, the transfer of the CH3-group from the methylated MT i requires MT2. 

The requirement of a second noncorrinoid protein in these two systems fromM barkeri and Cl. thermoaceticum reemphasizes the intriguing mix of similarities and differences in these three Cba-dependent methyl transferases. Thus, HCM is unique among the three in not requiring a second protein. Of course, the corrinoid iron-sulfur protein is unique in possessing a 4Fe-4S cluster. 

Menon, S., and Ragsdale, S. W., 1998, Role of the [4Ee64S] cluster in reductive activation of the cobalt center of the corrinoid iron-sulfur protein from Clostridium thermoaceticum during acetyl-CoA synthesis Biochem. 37(16) 5689n5698. 

ACS catalyzes the synthesis of acetyl-CoA from CO, CoA, and a methyl group donated by a methylated corrinoid iron sulfur protein (Reaction 4, Table 1). In the CODH-only enzymes like CODHI and II from C hydrogenoformans and R. rubrum, there is evidence for a channel between the surface and the C-cluster (above). On the other hand, in CODH/ACS,... 

The synthesis of acetyl-CoA by the Ljungdahl-Wood pathway of autotrophic carbon fixation in diverse bacteria and archaea is catalyzed by a Co- and Fe-containing corrinoid iron-sulfur protein (CoFeSP). This protein participates in the transfer of a methyl group from A -methyltetrahydrofolate to the cob(I)amide of CoFeSP to give a methylcob(III)amide, from which the methyl group is transferred to the reduced Ni-Ni-(4Fe-4S) active site cluster A of acetyl-CoA synthase (27). 

Svetlitchnaia T, Svetlitchnyi V, Meyer O, Dobbek H. Structural insights into methyltransfer reactions of a corrinoid iron-sulfur protein involved in acetyl-CoA synthesis. Proc. Natl. Acad. Sci. U.S.A. 2006 103 14331-14336. 

Ragsdale SW, Lindahl PA, Miinck E (1987) Mossbauer, EPR, and optical studies of the corrinoid/ iron-sulfur protein involved in the synthesis of acetyl coenzyme A by Clostridium thermoaceticum. J Biol Chem 262 14289-14297... 

The bifunctional carbon monoxide dehydrogenase (CODH)/acetyl-CoA synthase enzyme is a key enzyme involved in the Wood-Ljungdahl pathway of carbon fixation that operates in anaerobic bacteria. As such, it is a major player in the global carbon cycle. The CODH component of the enzyme catalyzes the reversible reduction of CO2 to CO (Equation (15)), which is then channeled to the ACS active site where it reacts with CoA and a methyl group provided by the corrinoid iron-sulfur protein (CFeSP) to form acetyl-CoA 30 (Equation (16)). 

All known ACS enzymes are bifunctional in that they possess a C cluster with COdFI activity in addition to an A cluster (the ACS active site. Scheme 9). In the enzymes, a CO tunnel is described through which GO can pass directly from the C cluster, where it is generated from CO2, to the A cluster, where acetyl GoA synthesis takes place. Again, two mechanisms were proposed that differ in the order of binding events and redox states involved. In essence, however, GO binds to an Ni-GHs species, followed by insertion and generation of an Ni-acetyl species, which upon reaction with GoA liberates the acetyl GoA product. It is interesting to note that methylation of Ni occurs by reaction with methyl cobalamin (Scheme 7). In M. thermoacetica, the cobalamin is the cofactor for a rather unique protein called the corrinoid iron sulfur protein (GFeSP). The above process, even if mechanistic details still remain in question, resembles the industrial Monsanto acetic acid synthesis process (Scheme 9, bottom). In this case, however, the reaction is catalyzed by a low-valent Rh catalyst. 

Zhao, S. Y Ragsdale, S. W. A conformational change in the methyltransferase from Clostridium thermoaceticum facilitates the methyl transfer from (6S)-methyltetrahydro-folate to the corrinoid iron-sulfur protein in the acetyl-CoA pathway. Biochemistry, 1996, 35(7), 2476-2481. 

Alignment of the MetH sequence between residues 366 and -610 with a methyltetrahydrofolate corrinoid iron-sulfur protein methyltransferase (AcsE) reveals 22% identity and 43% homology between these proteins (6) the same region of MetH is more distantly related to pteroate synthase (6, 31). Structures for pteroate synthase (52, 55) and the recently determined structure of AcsE (6) predict that the folate binding module will be a (Pa)g barrel. Model-building (6)... 

The bacterial metalloenzyme acetyl coenzyme A synthase/CO dehydrogenase (ACS/CODH) catalyzes two very important biological processes, namely the reduction of atmospheric CO2 to CO and the synthesis of acetyl coerrzyme A from CO, a methyl from a methylated corrinoid iron-sulfur protein, and the thiol coenzyme A [166-168]. This bifunctional errzyme is the key to the Wood-Ljiungahl pathway of anaerobic CO2 fixation (Scheme 1.18) and a major component of the global carbon cycle. Reactions catalyzed by CODH and ACS are shown in Eqs. (1.4) and (1.5) below. 

Central to acetogenesis [94], acetyl CoA synthase (ACS) effectively catalyzes the formation of acetyl CoA from CO and a cobalamin-like methyl carrier called the corrinoid iron sulfur protein (CoFeSP) (Eq. 12.8). 

CODH is unusual in that it can bring about two reactions (e.g., Eqs. 16.37 and 16.39) that are particularly interesting to the organometallic chemist the reduction of atmospheric CO2 to CO (CODH reaction, Eq. 16.37) and the synthesis of acetyl coenzyme A (ACS reaction, Eq. 16.39) from CO, a CH3 group taken from a corrinoid iron-sulfur protein (denoted CoFeSP in the equation), and coenzyme A, a thiol. These are analogous to reactions we have seen earlier the water-gas shift reaction (Eq. 16.36) and the Monsanto acetic acid process (Eq. 16.38). 

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