Mechanism of Ni,Fe-Containing Carbon Monoxide Dehydrogenases

Carbon monoxide dehydrogenases catalyze the reversible oxidation of CO with water to CO2, two protons and two electrons. Phylogenetically diverse bacteria and archaea living under anaerobic conditions employ different classes of Ni,Fe-containing carbon monoxide dehydrogenases to use CO as an energy source or to contribute in converting CO2 to acetyl-CoA. The active site of carbon monoxide dehydrogenases contains a unique [NiFe4S4]-cluster, the only known example in nature where Ni is integrated into a heterocubane structure. The Ni ion serves as the catalytic nucleophilic center for activating CO and CO2, in which it is supported by an electrophilic Fe ion placed in exo to the heterocubane cluster. This review gives an overview on current ideas how Ni,Fe-containing carbon monoxide dehydrogenases reversibly oxidize CO to CO2, with a focus on recent structural studies of the enzymes.