Double Cubane Cluster Protein and Its Reductase

Abstract

Abstract Chemically demanding reductions in biology may be achieved by coupling electron transfer to ATP hydrolysis. To achieve a unidirectional electron transfer against a redox‐potential gradient, the double‐cubane cluster‐containing protein (DCCP) forms a complex with an ATP‐dependent reductase, which couples ATP hydrolysis with electron transfer from its [4Fe4S] cluster to the active site of DCCP. DCCP has been named after its cofactor, containing two cubane‐type [4Fe4S] clusters linked by a μ‐sulfido ligand. The double‐cubane cluster is coordinated by six conserved cysteine residues, with both [4Fe4S] subclusters experiencing different environments. While the physiological substrate of DCCP is unknown, it catalyzes the nonphysiological reduction of acetylene, azide, and hydrazine. DCCP and its reductase are homologous to atypical dehydratases and class‐I benzoyl‐CoA reductases and share mechanistic analogies with nitrogenases and reductive activators of corrinoid proteins.