A Morphing [4Fe 3S nO] Cluster within a Carbon Monoxide Dehydrogenase Scaffold

Ni,Fe containing carbon monoxide dehydrogenases CODHs catalyze the reversible reduction of CO2 to CO. Several anaerobic microorganisms encode multiple CODHs in their genome, of which some, despite being annotated as CODHs, lack a cysteine of the canonical binding motif for the active site Ni,Fe cluster. Here, we report on the structure and reactivity of such a deviant enzyme, termed CooS VCh. Its structure reveals the typical CODH scaffold, but contains an iron sulfur oxo hybrid cluster. Although closely related to true CODHs, CooS VCh catalyzes neither CO oxidation, nor CO2 reduction. The active site of CooS VCh undergoes a redox dependent restructuring between a reduced [4Fe 3S] cluster and an oxidized [4Fe 2S S 2O 2 H2O ] cluster. Hydroxylamine, a slow turnover substrate of CooS VCh, oxidizes the hybrid cluster in two structurally distinct steps. Overall, minor changes in CODHs are sufficient to accommodate a Fe S O cluster in place of the Ni,Fe heterocubane cluster of CODH