The role of an iron-sulfur cluster in an enzymatic methylation reaction - Methylation of CO dehydrogenase/acetyl-CoA synthase by the methylated corrinoid iron-sulfur protein

This paper focuses on how a methyl group is transferred from a methyl-cobal t(III) species on one protein (the corrinoid iron-sulfur protein (CFeSP)) t o a nickel iron-sulfur cluster on another protein (carbon monoxide dehydrog enase/acetyl-CoA synthase). This is an essential step in the Wood-Ljungdahl pathway of anaerobic CO and CO2 fixation. The results described here stron gly indicate that transfer of methyl group to carbon monoxide dehydrogenase /acetyl-CoA synthase occurs by an S(N)2 pathway. They also provide convinci ng evidence that oxidative inactivation of Co(I) competes with methylation. Under the conditions of our anaerobic assay, Co(I) escapes from the cataly tic cycle one in every 100 turnover cycles. Reductive activation of the CFe SP is required to regenerate Co(I) and recruit the protein back into the ca talytic cycle. Our results strongly indicate that the [4Fe-4S] cluster of t he CFeSP is required for reductive activation. They support the hypothesis that the [4Fe-4S] cluster of the CFeSP does not participate directly in the methyl transfer step but provides a conduit for electron flow from physiol ogical reductants to the cobalt center.