9c0q
Carbon monoxide dehydrogenase (CODH) from Methanosarcina thermophila, specimen prepared on blot plunger
Structural highlights
FunctionACDA2_METTE Part of the ACDS complex that catalyzes the reversible cleavage of acetyl-CoA, allowing growth on acetate as sole source of carbon and energy. The alpha-epsilon subcomponent functions as a carbon monoxide dehydrogenase.[HAMAP-Rule:MF_01137] Publication Abstract from PubMedApproximately two-thirds of the estimated one-billion metric tons of methane produced annually by methanogens is derived from the cleavage of acetate. Acetate is broken down by a Ni-Fe-S-containing A-cluster within the enzyme acetyl-CoA synthase (ACS) to carbon monoxide (CO) and a methyl group (CH(3)(+)). The methyl group ultimately forms the greenhouse gas methane, whereas CO is converted to the greenhouse gas carbon dioxide (CO(2)) by a Ni-Fe-S-containing C-cluster within the enzyme carbon monoxide dehydrogenase (CODH). Although structures have been solved of CODH/ACS from acetogens, which use these enzymes to make acetate from CO(2), no structure of a CODH/ACS from a methanogen has been reported. In this work, we use cryo-electron microscopy to reveal the structure of a methanogenic CODH and CODH/ACS from Methanosarcina thermophila (MetCODH/ACS). We find that the N-terminal domain of acetogenic ACS, which is missing in all methanogens, is replaced by a domain of CODH. This CODH domain provides a channel for CO to travel between the two catalytic Ni-Fe-S clusters. It generates the binding surface for ACS and creates a remarkably similar CO alcove above the A-cluster using residues from CODH rather than ACS. Comparison of our MetCODH/ACS structure with our MetCODH structure reveals a molecular mechanism to restrict gas flow from the CO channel when ACS departs, preventing CO escape into the cell. Overall, these long-awaited structures of a methanogenic CODH/ACS reveal striking functional similarities to their acetogenic counterparts despite a substantial difference in domain organization. Capturing a methanogenic carbon monoxide dehydrogenase/acetyl-CoA synthase complex via cryogenic electron microscopy.,Biester A, Grahame DA, Drennan CL Proc Natl Acad Sci U S A. 2024 Oct 8;121(41):e2410995121. doi: , 10.1073/pnas.2410995121. Epub 2024 Oct 3. PMID:39361653[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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