Disease relevance of Moth_0835

• Cloning and expression of the gene cluster encoding key proteins involved in acetyl-CoA synthesis in Clostridium thermoaceticum: CO dehydrogenase, the corrinoid/Fe-S protein, and methyltransferase [1].
• The methyltransferase is expressed in E. coli in a fully active dimeric form with a specific activity and heat stability similar to the enzyme expressed in C. thermoaceticum [1].

High impact information on Moth_0835

• Key enzymes in the pathway are a methyltransferase, a corrinoid/Fe-S protein, a disulfide reductase, and a carbon monoxide dehydrogenase [1].
• The corrinoid protein is methylated in the presence of methyltransferase and methyltetrahydrofolate; methylation is on the cobalt of the corrinoid moiety of the protein [2].
• Binding of (6R,S)-methyltetrahydrofolate to methyltransferase from Clostridium thermoaceticum: role of protonation of methyltetrahydrofolate in the mechanism of methyl transfer [3].
• The pH dependence of the chemical shift in the 13C NMR spectrum for the N5-methyl resonance indicates that MeTr decreases the acidity of the N5 tertiary amine of CH3-H4folate by 1 pK unit in both water and deuterium oxide [3].
• The combined results indicate that CH3-H4folate binds to a hydrophobic region in MeTr that includes a tryptophan residue(s) [4].

Chemical compound and disease context of Moth_0835

• Regions in the sequence of MeTr and the E. coli cobalamin-dependent methionine synthase were found to share significant homology, suggesting that they may represent tetrahydrofolate-binding domains [5].

Biological context of Moth_0835

• It is quite open in MeTr, where it can be modeled as the cobalamin binding site [6].

Associations of Moth_0835 with chemical compounds

• This manuscript describes the isolation of the genes that code for the methyltransferase, the two subunits of the corrinoid/Fe-S protein, and the two subunits of carbon monoxide dehydrogenase [1].
• Methylation of cobalamin (B12) is catalyzed by the methyltransferase but methylcobalamin does not substitute for the methylated corrinoid protein as the source of methyl in the formation of acetyl-CoA [2].
• By measuring the dependence of the O-demethylation reaction on purified enzymes of the acetyl-CoA pathway, it was established that CO dehydrogenase, the corrinoid/iron-sulfur protein, and methyltransferase all were required for acetyl-CoA formation [7].
• Western blots analyses showed that nitrate also decreased the levels of the corrinoid iron-sulfur protein (60%) and methyltransferase (70%) [8].
• The methyltransferase catalyzes the transfer of the methyl group to the methyl acceptor, and the CO is converted to a formyl derivative by the CO dehydrogenase [9].

References